You are on page 1of 138

Introduction to Cell Biology

A Guide for IVMS AP High School Health

Sciences| Pre-Med. Track Learners

Compiled by Marc Imhotep Cray, M.D.(12-13)

Click here to open companion Web page| w Video Animations Playlist

IVMS VLog|From NDSU Virtual Cell Animations Project

Cell (biology) Cell membrane Cytosol Cytoplasm Organelle Cell nucleus Nucleolus Ribosome Vesicle (biology and chemistry) Endoplasmic reticulum Golgi apparatus Cytoskeleton Mitochondrion Vacuole Lysosome Centrosome DNA Genome 1 13 20 26 28 34 48 51 57 62 66 70 74 91 94 97 101 119

Article Sources and Contributors Image Sources, Licenses and Contributors 126 133

Article Licenses
License 136

Cell (biology)

Cell (biology)

Onion (Allium) cells in different phases of the cell cycle

The cells of eukaryotes (left) and prokaryotes (right)

The cell is the basic structural, functional and biological unit of all known living organisms. Cells are the smallest unit of life that can replicate independently, and are often called the "building blocks of life". Cells consist of a protoplasm enclosed within a membrane, which contains many biomolecules such as proteins and nucleic acids.[1] Organisms can be classified as unicellular (consisting of a single cell; including most bacteria) or multicellular (including plants and animals). While the number of cells in plants and animals varies from species to species, humans contain about 100 trillion (1014) cells. Most plant and animal cells are visible only under the microscope, with dimensions between 1 and 100micrometres. The cell was discovered by Robert Hooke in 1665. The cell theory, first developed in 1839 by Matthias Jakob Schleiden and Theodor Schwann, states that all organisms are composed of one or more cells, that all cells come from preexisting cells, that vital functions of an organism occur within cells, and that all cells contain the hereditary information necessary for regulating cell functions and for transmitting information to the next generation of cells. Cells emerged on Earth at least 3.5 billion years ago. The word cell comes from the Latin cella, meaning "small room". It was coined by Robert Hooke in his book Micrographia (1665), in which he compared the cork cells he saw through his microscope to the small rooms monks lived in.[2]

There are two types of cells, eukaryotes, which contain a nucleus, and prokaryotes, which do not. Prokaryotic cells are usually single-celled organisms, while eukaryotic cells can be either single-celled or part of multicellular organisms.

Cell (biology)

Table 1: Comparison of features of prokaryotic and eukaryotic cells

Prokaryotes Typical organisms Typical size Type of nucleus DNA bacteria, archaea ~ 15 m protists, fungi, plants, animals ~ 10100 m Eukaryotes

nucleoid region; no true nucleus true nucleus with double membrane circular (usually) linear molecules (chromosomes) with histone proteins RNA synthesis in the nucleus protein synthesis in the cytoplasm 60S and 40S highly structured by endomembranes and a cytoskeleton flagella and cilia containing microtubules; lamellipodia and filopodia containing actin one to several thousand (though some lack mitochondria) in algae and plants single cells, colonies, higher multicellular organisms with specialized cells

RNA/protein synthesis coupled in the cytoplasm


50S and 30S

Cytoplasmic structure very few structures Cell movement Mitochondria Chloroplasts Organization Cell division flagella made of flagellin none none usually single cells

Binary fission (simple division) Mitosis (fission or budding) Meiosis

Prokaryotic cells
Prokaryotic cells were the first form of life on Earth. They are simpler and smaller than eukaryotic cells, and lack membrane-bound organelles such as the nucleus. Prokaryotes include two of the domains of life, bacteria and archaea. The DNA of a prokaryotic cell consists of a single chromosome that is in direct contact with the cytoplasm. The nuclear region in the cytoplasm is called the nucleoid. A prokaryotic cell has three architectural regions: On the outside, flagella and pili project from the cell's surface. These are structures (not present in all prokaryotes) made of proteins that facilitate movement and communication between cells.

Diagram of a typical prokaryotic cell

Enclosing the cell is the cell envelope generally consisting of a cell wall covering a plasma membrane though some bacteria also have a further covering layer called a capsule. The envelope gives rigidity to the cell and separates the interior of the cell from its environment, serving as a protective filter. Though most prokaryotes have a cell wall, there are exceptions such as Mycoplasma (bacteria) and Thermoplasma (archaea). The cell wall consists of peptidoglycan in bacteria, and acts as an additional barrier against exterior forces. It also prevents the cell from expanding and bursting (cytolysis) from osmotic pressure due to a hypotonic environment. Some eukaryotic cells (plant cells and fungal cells) also have a cell wall.

Cell (biology) Inside the cell is the cytoplasmic region that contains the genome (DNA), ribosomes and various sorts of inclusions. The prokaryotic chromosome is usually a circular molecule (an exception is that of the bacterium Borrelia burgdorferi, which causes Lyme disease).[3] Though not forming a nucleus, the DNA is condensed in a nucleoid. Prokaryotes can carry extrachromosomal DNA elements called plasmids, which are usually circular. Plasmids encode additional genes, such as antibiotic resistance genes.

Eukaryotic cells
Plants, animals, fungi, slime moulds, protozoa, and algae are all eukaryotic. These cells are about fifteen times wider than a typical prokaryote and can be as much as a thousand times greater in volume. The main distinguishing feature of eukaryotes as compared to prokaryotes is compartmentalization: the presence of membrane-bound compartments in which specific metabolic activities take place. Most important among these is a cell nucleus, a membrane-delineated compartment that houses the eukaryotic cell's DNA. This nucleus gives the eukaryote its name, which means "true nucleus." Other differences include: The plasma membrane resembles that of prokaryotes in function, with minor differences in the setup. Cell walls may or may not be present. The eukaryotic DNA is organized in one or more linear molecules, called chromosomes, which are associated with histone proteins. All chromosomal DNA is stored in the cell nucleus, separated from the cytoplasm by a membrane. Some eukaryotic organelles such as mitochondria also contain some DNA. Many eukaryotic cells are ciliated with primary cilia. Primary cilia play important roles in chemosensation, mechanosensation, and thermosensation. Cilia may thus be "viewed as a sensory cellular antennae that coordinates a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation." Eukaryotes can move using motile cilia or flagella. Eukaryotic flagella are less complex than those of prokaryotes.

Structure of a typical animal cell

Structure of a typical plant cell

Table 2: Comparison of structures between animal and plant cells

Typical animal cell Typical plant cell

Cell (biology)

Organelles Nucleus Nucleolus (within the nucleus) Rough endoplasmic reticulum (ER) Smooth endoplasmic reticulum Ribosomes Cytoskeleton Golgi apparatus Cytoplasm Mitochondria Vesicles Lysosomes Centrosome Centrioles Nucleus Nucleolus (within the nucleus) Rough endoplasmic reticulum Smooth endoplasmic reticulum Ribosomes Cytoskeleton Golgi apparatus (dictiosomes) Cytoplasm Mitochondria Plastids and their derivatives Vacuole(s) Cell wall

Subcellular components
All cells, whether prokaryotic or eukaryotic, have a membrane that envelops the cell, separates its interior from its environment, regulates what moves in and out (selectively permeable), and maintains the electric potential of the cell. Inside the membrane, a salty cytoplasm takes up most of the cell volume. All cells (except red blood cells which lack a cell nucleus and most organelles to accommodate maximum space for hemoglobin) possess DNA, the hereditary material of genes, and RNA, containing the information necessary to build various proteins such as enzymes, the cell's primary machinery. There are also other kinds of biomolecules in cells. This article lists these primary components of the cell, then briefly describes their function.


Illustration depicting major structures inside an eukaryotic animal cell

The cell membrane, or plasma membrane, surrounds the cytoplasm of a cell. In animals, the plasma membrane is the outer boundary of the cell, while in plants and prokaryotes it is usually covered by a cell wall. This membrane serves to separate and protect a cell from its surrounding environment and is made mostly from a double layer of phospholipids, which are amphiphilic (partly hydrophobic and partly hydrophilic). Hence, the layer is called a phospholipid bilayer, or sometimes a fluid mosaic membrane. Embedded within this membrane is a variety of protein molecules that act as channels and pumps that move different molecules into and out of the cell. The membrane is said to be 'semi-permeable', in that it can either let a substance (molecule or ion) pass through freely, pass through to a limited extent or not pass through at all. Cell surface membranes also contain receptor proteins that allow cells to detect external signaling molecules such as hormones.

Cell (biology)

The cytoskeleton acts to organize and maintain the cell's shape; anchors organelles in place; helps during endocytosis, the uptake of external materials by a cell, and cytokinesis, the separation of daughter cells after cell division; and moves parts of the cell in processes of growth and mobility. The eukaryotic cytoskeleton is composed of microfilaments, intermediate filaments and microtubules. There are a great number of proteins associated with them, each controlling a cell's structure by directing, bundling, and aligning filaments. The prokaryotic cytoskeleton is less well-studied but is involved in the maintenance of cell shape, polarity and cytokinesis.

A fluorescent image of an endothelial cell. Nuclei are stained blue, mitochondria are stained red, and microfilaments are stained green.

Genetic material
Two different kinds of genetic material exist: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Most cells use DNA for their long-term information storage. The biological information contained in an organism is encoded in its DNA sequence. RNA is used for information transport (e.g., mRNA) and enzymatic functions (e.g., ribosomal RNA). Transfer RNA (tRNA) molecules are used to add amino acids during protein translation. Prokaryotic genetic material is organized in a simple circular DNA molecule (the bacterial chromosome) in the nucleoid region of the cytoplasm. Eukaryotic genetic material is divided into different, linear molecules called chromosomes inside a discrete nucleus, usually with additional genetic material in some organelles like mitochondria and chloroplasts (see endosymbiotic theory). A human cell has genetic material contained in the cell nucleus (the nuclear genome) and in the mitochondria (the mitochondrial genome). In humans the nuclear genome is divided into 46 linear DNA molecules called chromosomes, including 22 homologous chromosome pairs and a pair of sex chromosomes. The mitochondrial genome is a circular DNA molecule distinct from the nuclear DNA. Although the mitochondrial DNA is very small compared to nuclear chromosomes, it codes for 13 proteins involved in mitochondrial energy production and specific tRNAs. Foreign genetic material (most commonly DNA) can also be artificially introduced into the cell by a process called transfection. This can be transient, if the DNA is not inserted into the cell's genome, or stable, if it is. Certain viruses also insert their genetic material into the genome.

Organelles are parts of the cell which are adapted and/or specialized for carrying out one or more vital functions, analogous to the organs of the human body (such as the heart, lung, and kidney, with each organ performing a different function). Both eukaryotic and prokaryotic cells have organelles, but prokaryotic organelles are generally simpler and are not membrane-bound. There are several types of organelles in a cell. Some (such as the nucleus and golgi apparatus) are typically solitary, while others (such as mitochondria, chloroplasts, peroxisomes and lysosomes) can be numerous (hundreds to thousands). The cytosol is the gelatinous fluid that fills the cell and surrounds the organelles.

Cell (biology) Eukaryotic Cell nucleus: A cell's information center, the cell nucleus is the most conspicuous organelle found in a eukaryotic cell. It houses the cell's chromosomes, and is the place where almost all DNA replication and RNA synthesis (transcription) occur. The nucleus is spherical and separated from the cytoplasm by a double membrane called the nuclear envelope. The nuclear envelope isolates and protects a cell's DNA from various molecules that could accidentally damage its structure or interfere with its processing. During processing, DNA is transcribed, or copied into a special RNA, called messenger RNA (mRNA). This mRNA is then transported out of the nucleus, where it is translated into a specific protein molecule. The nucleolus is a specialized region within the nucleus where ribosome subunits are assembled. In prokaryotes, DNA processing takes place in the cytoplasm. Mitochondria and Chloroplasts: the power generators: Mitochondria are self-replicating organelles that occur in various numbers, shapes, and sizes in the cytoplasm of all eukaryotic cells. Mitochondria play a critical role in generating energy in the eukaryotic cell. Respiration occurs in the cell mitochondria, which generate the cell's energy by oxidative phosphorylation, using oxygen to release energy stored in cellular nutrients (typically pertaining to glucose) to generate ATP. Mitochondria multiply by binary fission, like prokaryotes. Chloroplasts can only be found in plants and algae, and they capture the sun's energy to make ATP. Endoplasmic reticulum: The endoplasmic reticulum (ER) is a transport network for molecules targeted for certain modifications and specific destinations, as compared to molecules that float freely in the cytoplasm. The ER has two forms: the rough ER, which has ribosomes on its surface that secrete proteins into the ER, and the smooth ER, which lacks ribosomes. The smooth ER plays a role in calcium sequestration and release. (See Endoplasmic reticulum) Golgi apparatus: The primary function of the Golgi apparatus is to process and package the macromolecules such as proteins and lipids that are synthesized by the cell. (See Golgi apparatus) Lysosomes and Peroxisomes: Lysosomes contain digestive enzymes (acid hydrolases). They digest excess or worn-out Diagram of an endomembrane system organelles, food particles, and engulfed viruses or bacteria. Peroxisomes have enzymes that rid the cell of toxic peroxides. The cell could not house these destructive enzymes if they were not contained in a membrane-bound system. (See Lysosome and Peroxisome) Centrosome the cytoskeleton organiser: The centrosome produces the microtubules of a cell a key component of the cytoskeleton. It directs the transport through the ER and the Golgi apparatus. Centrosomes are composed of two centrioles, which separate during cell division and help in the formation of the mitotic spindle. A single centrosome is present in the animal cells. They are also found in some fungi and algae cells. (See Centrosome) Vacuoles: Vacuoles store food and waste. Some vacuoles store extra water. They are often described as liquid filled space and are surrounded by a membrane. Some cells, most notably Amoeba, have contractile vacuoles, which can pump water out of the cell if there is too much water. The vacuoles of eukaryotic cells are usually larger in those of plants than animals. (See Vacuole)

Cell (biology) Eukaryotic and prokaryotic Ribosomes: The ribosome is a large complex of RNA and protein molecules. They each consist of two subunits, and act as an assembly line where RNA from the nucleus is used to synthesise proteins from amino acids. Ribosomes can be found either floating freely or bound to a membrane (the rough endoplasmatic reticulum in eukaryotes, or the cell membrane in prokaryotes).

Structures outside the cell membrane

Many cells also have structures which exist wholly or partially outside the cell membrane. These structures are notable because they are not protected from the external environment by the impermeable cell membrane. In order to assemble these structures, their components must be carried across the cell membrane by export processes.

Cell wall
Many types of prokaryotic and eukaryotic cells have a cell wall. The cell wall acts to protect the cell mechanically and chemically from its environment, and is an additional layer of protection to the cell membrane. Different types of cell have cell walls made up of different materials; plant cell walls are primarily made up of pectin, fungi cell walls are made up of chitin and bacteria cell walls are made up of peptidoglycan.

Capsule A gelatinous capsule is present in some bacteria outside the cell membrane and cell wall. The capsule may be polysaccharide as in pneumococci, meningococci or polypeptide as Bacillus anthracis or hyaluronic acid as in streptococci. (See Bacterial capsule.) Capsules are not marked by normal staining protocols and can be detected by India ink or Methyl blue; which allows for higher contrast between the cells for observation.:87 Flagella Flagella are organelles for cellular mobility. The bacterial flagellum stretches from cytoplasm through the cell membrane(s) and extrudes through the cell wall. They are long and thick thread-like appendages, protein in nature. Are most commonly found in bacteria cells but are found in animal cells as well. Fimbriae (pili) They are short and thin hair-like filaments, formed of protein called pilin (antigenic). Fimbriae are responsible for attachment of bacteria to specific receptors of human cell (adherence). There are special types of pili called (sex pili) involved in conjunction. (See Pilus.)

Growth and metabolism

Between successive cell divisions, cells grow through the functioning of cellular metabolism. Cell metabolism is the process by which individual cells process nutrient molecules. Metabolism has two distinct divisions: catabolism, in which the cell breaks down complex molecules to produce energy and reducing power, and anabolism, in which the cell uses energy and reducing power to construct complex molecules and perform other biological functions. Complex sugars consumed by the organism can be broken down into a less chemically complex sugar molecule called glucose. Once inside the cell, glucose is broken down to make adenosine triphosphate (ATP), a form of energy, through two different pathways. The first pathway, glycolysis, requires no oxygen and is referred to as anaerobic metabolism. Each reaction produces ATP and NADH, which are used in cellular functions, as well as two pyruvate molecules that derive from the original glucose molecule. In prokaryotes, all energy is produced by glycolysis.

Cell (biology) The second pathway, called the Krebs cycle or citric acid cycle, is performed only by eukaryotes and involves further breakdown of the pyruvate produced in glycolysis. It occurs inside the mitochondria and generates much more energy than glycolysis, mostly through oxidative phosphorylation.

Cell division involves a single cell (called a mother cell) dividing into two daughter cells. This leads to growth in multicellular organisms (the growth of tissue) and to procreation (vegetative reproduction) in unicellular organisms. Prokaryotic cells divide by binary fission, while eukaryotic cells usually undergo a process of nuclear division, called mitosis, followed by division of the cell, called cytokinesis. A diploid cell may also undergo meiosis to produce haploid cells, usually four. Haploid cells serve as gametes in multicellular organisms, fusing to form new diploid cells. DNA replication, or the process of duplicating a cell's genome, always happens when a cell divides through mitosis or binary fission. This occurs during the S phase of the cell cycle.

In meiosis, the DNA is replicated only once, while the cell divides twice. DNA replication only occurs before meiosis I. DNA replication does not occur when the cells divide the second time, in meiosis II. Replication, like all cellular activities, requires specialized proteins for carrying out the job.

Bacteria divide by binary fission, while eukaryotes divide by mitosis or meiosis.

Cell (biology)

Protein synthesis
Cells are capable of synthesizing new proteins, which are essential for the modulation and maintenance of cellular activities. This process involves the formation of new protein molecules from amino acid building blocks based on information encoded in DNA/RNA. Protein synthesis generally consists of two major steps: transcription and translation. Transcription is the process where genetic information in DNA is used to produce a complementary RNA strand. This RNA strand is then processed to give messenger RNA (mRNA), which is free to migrate through the cell. mRNA molecules bind to protein-RNA complexes called ribosomes located in the cytosol, where they are translated into polypeptide sequences. The ribosome mediates the formation of a polypeptide sequence based on the mRNA sequence. The mRNA sequence directly relates to the polypeptide sequence by binding to transfer RNA (tRNA) adapter molecules in binding pockets within the ribosome. The new polypeptide then folds into a functional three-dimensional protein molecule.

Movement or motility
Cells can move during many processes: such as wound healing, the immune response and cancer metastasis. For wound healing to occur, white blood cells and cells that ingest bacteria move to the wound site to kill the microorganisms that cause infection. At the same time fibroblasts (connective tissue cells) move there to remodel damaged structures. In the case of tumor development, cells from a primary tumor move away and spread to other parts of the body. Cell motility involves many receptors, crosslinking, bundling, binding, adhesion, motor and other proteins. The process is divided into three steps protrusion of the leading edge of the cell, adhesion of the leading edge and de-adhesion at the cell body and rear, and cytoskeletal contraction to pull the cell forward. Each step is driven by physical forces generated by unique segments of the cytoskeleton.[4][5]

The origin of cells has to do with the origin of life, which began the history of life on Earth.

An overview of protein synthesis.Within the nucleus of the cell (light blue), genes (DNA, dark blue) are transcribed into RNA. This RNA is then subject to post-transcriptional modification and control, resulting in a mature mRNA (red) that is then transported out of the nucleus and into the cytoplasm (peach), where it undergoes translation into a protein. mRNA is translated by ribosomes (purple) that match the three-base codons of the mRNA to the three-base anti-codons of the appropriate tRNA. Newly synthesized proteins (black) are often further modified, such as by binding to an effector molecule (orange), to become fully active.

Cell (biology)


Origin of the first cell

There are several theories about the origin of small molecules that led to life on the early Earth. They may have been carried to Earth on meteorites (see Murchison meteorite), created at deep-sea vents, or synthesized by lightning in a reducing atmosphere (see MillerUrey experiment). There is little experimental data defining what the first self-replicating forms were. RNA is thought to be the earliest self-replicating molecule, as it is capable of both storing genetic information and catalyzing chemical reactions (see RNA world hypothesis), but some other entity with the potential to self-replicate could have preceded RNA, such as clay or peptide nucleic acid.

Cells emerged at least 3.5 billion years ago.[][] The current belief is that these cells were heterotrophs. The early cell membranes were probably more simple and permeable than modern ones, with only a single fatty acid chain per lipid. Lipids are known to spontaneously form bilayered vesicles in water, and could have preceded RNA, but the first cell membranes could also have been produced by catalytic RNA, or even have required structural proteins before they could form.

Stromatolites are left behind by cyanobacteria, also called blue-green algae. They are the oldest known fossils of life on Earth. This one-billion-year-old fossil is from Glacier National Park in the United States.

Origin of eukaryotic cells

The eukaryotic cell seems to have evolved from a symbiotic community of prokaryotic cells. DNA-bearing organelles like the mitochondria and the chloroplasts are descended from ancient symbiotic oxygen-breathing proteobacteria and cyanobacteria, respectively, which were endosymbiosed by an ancestral archaean prokaryote. There is still considerable debate about whether organelles like the hydrogenosome predated the origin of mitochondria, or vice versa: see the hydrogen hypothesis for the origin of eukaryotic cells. Sex, as the stereotyped choreography of meiosis and syngamy that persists in nearly all extant eukaryotes, may have played a role in the transition from prokaryotes to eukaryotes. One view, on the origin of sex in eukaryotic cells, is that eukaryotic sex evolved from a prokaryotic sexual process termed transformation. According to this view, bacterial transformation is an adaptation for repairing DNA damages that arise during stressful conditions, and this role has been maintained in meiosis, where recombinational DNA repair is promoted. Thus the adaptive benefit of prokaryotic sex, recombinational repair, was maintained through the evolutionary transition from prokaryotes to single-celled eukaryotes.[6][7] This view is also presented in the Wikipedia articles Transformation (genetics), Evolution of sexual reproduction and Sex. In another view, an 'origin of sex as vaccination' theory suggests that the eukaryote genome accreted from prokaryan parasite genomes in numerous rounds of lateral gene transfer. Sex-as-syngamy (fusion sex) arose when infected hosts began swapping nuclearized genomes containing co-evolved, vertically transmitted symbionts that conveyed protection against horizontal infection by more virulent symbionts.

Cell (biology)


History of research
16321723: Antonie van Leeuwenhoek teaches himself to make lenses, constructs simple microscopes and draws protozoa, such as Vorticella from rain water, and bacteria from his own mouth. 1665: Robert Hooke discovers cells in cork, then in living plant tissue using an early compound microscope. 1839: Theodor Schwann and Matthias Jakob Schleiden elucidate the principle that plants and animals are made of cells, concluding that cells are a common unit of structure and development, and thus founding the cell theory. 1855: Rudolf Virchow states that new cells come from pre-existing cells by cell division (omnis cellula ex cellula). 1859: The belief that life forms can occur spontaneously (generatio spontanea) is contradicted by Louis Pasteur (18221895) (although Francesco Redi had performed an experiment in 1668 that suggested the same conclusion). 1931: Ernst Ruska builds the first transmission electron microscope (TEM) at the University of Berlin. By 1935, he has built an EM with twice the resolution of a light microscope, revealing previously unresolvable organelles. 1953: Watson and Crick made their first announcement on the double helix structure of DNA on February 28. 1981: Lynn Margulis published Symbiosis in Cell Evolution detailing the endosymbiotic theory.

[1] Cell Movements and the Shaping of the Vertebrate Body (http:/ / www. ncbi. nlm. nih. gov/ entrez/ query. fcgi?cmd=Search& db=books& doptcmdl=GenBookHL& term=Cell+ Movements+ and+ the+ Shaping+ of+ the+ Vertebrate+ Body+ AND+ mboc4[book]+ AND+ 374635[uid]& rid=mboc4. section. 3919) in Chapter 21 of Molecular Biology of the Cell (http:/ / www. ncbi. nlm. nih. gov/ entrez/ query. fcgi?cmd=Search& db=books& doptcmdl=GenBookHL& term=cell+ biology+ AND+ mboc4[book]+ AND+ 373693[uid]& rid=mboc4) fourth edition, edited by Bruce Alberts (2002) published by Garland Science. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos. It is also common to describe small molecules such as amino acids as " molecular building blocks (http:/ / www. ncbi. nlm. nih. gov/ entrez/ query. fcgi?cmd=Search& db=books& doptcmdl=GenBookHL& term="all+ cells"+ AND+ mboc4[book]+ AND+ 372023[uid]& rid=mboc4. section. 4#23)". [2] "... I could exceedingly plainly perceive it to be all perforated and porous, much like a Honey-comb, but that the pores of it were not regular [..] these pores, or cells, [..] were indeed the first microscopical pores I ever saw, and perhaps, that were ever seen, for I had not met with any Writer or Person, that had made any mention of them before this. . ." Hooke describing his observations on a thin slice of cork. Robert Hooke (http:/ / www. ucmp. berkeley. edu/ history/ hooke. html) [3] European Bioinformatics Institute, Karyn's Genomes: Borrelia burgdorferi (http:/ / www. ebi. ac. uk/ 2can/ genomes/ bacteria/ Borrelia_burgdorferi. html), part of 2can on the EBI-EMBL database. Retrieved 5 August 2012 [4] Alberts B, Johnson A, Lewis J. et al. Molecular Biology of the Cell, 4e. Garland Science. 2002 [5] Ananthakrishnan R, Ehrlicher A. The Forces Behind Cell Movement. Int J Biol Sci 2007; 3:303317. http:/ / www. biolsci. org/ v03p0303. htm [6] Bernstein H, Bernstein C. (2010) Evolutionary Origin of Recombination during Meiosis. BioScience 60(7):498-505. doi: http:/ / dx. doi. org/ 10. 1525/ bio. 2010. 60. 7. 5 [7] Bernstein H, Bernstein C, Michod RE (2012). DNA repair as the primary adaptive function of sex in bacteria and eukaryotes. Chapter 1: pp.1-49 in: DNA Repair: New Research, Sakura Kimura and Sora Shimizu editors. Nova Sci. Publ., Hauppauge, N.Y. ISBN 978-1-62100-808-8 https:/ / www. novapublishers. com/ catalog/ product_info. php?products_id=31918

This article incorporatespublic domain material from the NCBI document "Science Primer" (http://www.

Cell (biology)


External links
Inside the Cell ( - a science education booklet by National Institutes of Health, in PDF and ePub. Cells Alive! ( Cell Biology ( in "The Biology Project" of University of Arizona. Centre of the Cell online ( The Image & Video Library of The American Society for Cell Biology (, a collection of peer-reviewed still images, video clips and digital books that illustrate the structure, function and biology of the cell. HighMag Blog (, still images of cells from recent research articles. New Microscope Produces Dazzling 3D Movies of Live Cells ( html), March 4, 2011 - Howard Hughes Medical Institute. Interactive Visualization of the C. elegans Cell lineage ( Visualize the entire cell lineage tree of the nematode C. elegans

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). Molecular Biology of the Cell (http://www. (4th ed.). Garland. ISBN0-8153-3218-1. Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipurksy SL, Darnell J (2004). Molecular Cell Biology ( (5th ed.). WH Freeman: New York, NY. ISBN978-0-7167-4366-8. Cooper GM (2000). The cell: a molecular approach ( fcgi?rid=cooper.TOC&depth=2) (2nd ed.). Washington, D.C: ASM Press. ISBN0-87893-102-3.

Cell membrane


Cell membrane
The 'cell membrane' (also known as the plasma membrane or cytoplasmic membrane) is a biological membrane that separates the interior of all cells from the outside environment.[1] The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. The basic function of the cell membrane is to protect the cell from its surroundings. It consists of the phospholipid bilayer with embedded proteins. Cell membranes are involved in a variety of cellular processes such as cell adhesion, ion conductivity and cell signaling and serve as the attachment surface for several extracellular structures, including the cell wall, glycocalyx, and intracellular cytoskeleton. Cell membranes can be artificially reassembled.

Illustration of a Eukaryotic cell membrane

The cell membrane or plasma membrane surrounds the cytoplasm of living cells, physically separating the intracellular components from the extracellular environment. Fungi, bacteria and plants also have the cell wall which provides a mechanical support for the cell and precludes the passage of larger molecules. The cell A detailed diagram of the cell membrane membrane also plays a role in anchoring the cytoskeleton provide shape to the cell, and in attaching to the extracellular matrix and other cells to help group cells together to form tissues.

Cell membrane


The membrane is selectively permeable and able to regulate what enters and exits the cell, thus facilitating the transport of materials needed for survival. The movement of substances across the membrane can be either "passive", occurring without the input of cellular energy, or active, requiring the cell to expend energy in transporting it. The membrane also maintains the cell potential. The cell membrane thus works as a selective filter that allows only certain things to come inside or go outside the cell. The cell employs a number of transport mechanisms that involve biological membranes:

Illustration depicting cellular diffusion

1. Passive osmosis and diffusion: Some substances (small molecules, ions) such as carbon dioxide (CO2) and oxygen (O2), can move across the plasma membrane by diffusion, which is a passive transport process. Because the membrane acts as a barrier for certain molecules and ions, they can occur in different concentrations on the two sides of the membrane. Such a concentration gradient across a semipermeable membrane sets up an osmotic flow for the water. 2. Transmembrane protein channels and transporters: Nutrients, such as sugars or amino acids, must enter the cell, and certain products of metabolism must leave the cell. Such molecules are pumped across the membrane by transmembrane transporters or diffuse through protein channels such as Aquaporins (in the case of water (H2O)). These proteins, also called permeases, are usually quite specific, recognizing and transporting only a limited food group of chemical substances, often even only a single substance. 3. Endocytosis: Endocytosis is the process in which cells absorb molecules by engulfing them. The plasma membrane creates a small deformation inward, called an invagination, in which the substance to be transported is captured. The deformation then pinches off from the membrane on the inside of the cell, creating a vesicle containing the captured substance. Endocytosis is a pathway for internalizing solid particles (cell eating or phagocytosis), small molecules and ions (cell drinking or pinocytosis), and macromolecules. Endocytosis requires energy and is thus a form of active transport. 4. Exocytosis: Just as material can be brought into the cell by invagination and formation of a vesicle, the membrane of a vesicle can be fused with the plasma membrane, extruding its contents to the surrounding medium. This is the process of exocytosis. Exocytosis occurs in various cells to remove undigested residues of substances brought in by endocytosis, to secrete substances such as hormones and enzymes, and to transport a substance completely across a cellular barrier. In the process of exocytosis, the undigested waste-containing food vacuole or the secretory vesicle budded from Golgi apparatus, is first moved by cytoskeleton from the interior of the cell to the surface. The vesicle membrane comes in contact with the plasma membrane. The lipid molecules of the two bilayers rearrange themselves and the two membranes are, thus, fused. A passage is formed in the fused membrane and the vesicles discharges its contents outside the cell.

Cell membrane


Gram-negative bacteria have both a plasma membrane and an outer membrane separated by a periplasmic space. Other prokaryotes have only a plasma membrane. Prokaryotic cells are also surrounded by a cell wall composed of peptidoglycan (amino acids and sugars). Some eukaryotic cells also have cells walls, but none that are made of peptidoglycan.

Fluid mosaic model
According to the fluid mosaic model of S.J.Singer and G.L. Nicolson (1972), which replaced the earlier model of Davson and Danielli, biological membranes can be considered as a two-dimensional liquid in which lipid and protein molecules diffuse more or less easily. Although the lipid bilayers that form the basis of the membranes do indeed form two-dimensional liquids by themselves, the plasma membrane also contains a large quantity of proteins, which provide more structure. Examples of such structures are protein-protein complexes, pickets and fences formed by the actin-based cytoskeleton, and potentially lipid rafts.

Lipid bilayer
Lipid bilayers form through the process of self-assembly. The cell membrane consists primarily of a thin layer of amphipathic phospholipids which spontaneously arrange so that the hydrophobic "tail" regions are isolated from the surrounding polar fluid, causing the more hydrophilic "head" regions to associate with the intracellular (cytosolic) and extracellular faces of the resulting bilayer. This forms a continuous, spherical lipid bilayer. Forces such as van der Waals, electrostatic, hydrogen bonds, and noncovalent interactions all contribute to the formation of the lipid bilayer. Overall, hydrophobic interactions are the major driving force in the formation of lipid bilayers.

Diagram of the arrangement of amphipathic lipid molecules to form a lipid bilayer. The yellow polar head groups separate the grey hydrophobic tails from the aqueous cytosolic and extracellular environments.

Lipid bilayers are generally impermeable to ions and polar molecules. The arrangement of hydrophilic heads and hydrophobic tails of the lipid bilayer prevent polar solutes (ex. amino acids, nucleic acids, carbohydrates, proteins, and ions) from diffusing across the membrane, but generally allows for the passive diffusion of hydrophobic molecules. This affords the cell the ability to control the movement of these substances via transmembrane protein complexes such as pores, channels and gates. Flippases and scramblases concentrate phosphatidyl serine, which carries a negative charge, on the inner membrane. Along with NANA, this creates an extra barrier to charged moieties moving through the membrane. Membranes serve diverse functions in eukaryotic and prokaryotic cells. One important role is to regulate the movement of materials into and out of cells. The phospholipid bilayer structure (fluid mosaic model) with specific membrane proteins accounts for the selective permeability of the membrane and passive and active transport mechanisms. In addition, membranes in prokaryotes and in the mitochondria and chloroplasts of eukaryotes facilitate the synthesis of ATP through chemiosmosis.

Cell membrane


Membrane polarity
The apical membrane of a polarized cell is the surface of the plasma membrane that faces inward to the lumen. This is particularly evident in epithelial and endothelial cells, but also describes other polarized cells, such as neurons. The basolateral membrane of a polarized cell is the surface of the plasma membrane that forms its basal and lateral surfaces. It faces outwards, towards the interstitium, and away from the lumen. Basolateral membrane is a compound phrase referring to the terms "basal (base) membrane" and "lateral (side) membrane", which, especially Alpha intercalated cell in epithelial cells, are identical in composition and activity. Proteins (such as ion channels and pumps) are free to move from the basal to the lateral surface of the cell or vice versa in accordance with the fluid mosaic model. Tight junctions join epithelial cells near their apical surface to prevent the migration of proteins from the basolateral membrane to the apical membrane. The basal and lateral surfaces thus remain roughly equivalentWikipedia:Please clarify to one another, yet distinct from the apical surface.

Membrane structures
Cell membrane can form different types of "supramembrane" structures such as caveola, postsynaptic density, podosome, invadopodium, focal adhesion, and different types of cell junctions. These structures are usually responsible for cell adhesion, communication, endocytosis and exocytosis. They can be visualized by electron microscopy or fluorescence microscopy. They are composed of specific proteins, such as integrins and cadherins.

The cytoskeleton is found underlying the cell membrane in the cytoplasm and provides a scaffolding for membrane proteins to anchor to, as well as forming organelles that extend from the cell. Indeed, cytoskeletal elements interact extensively and intimately with the cell membrane. Anchoring proteins restricts them to a particular cell surface for example, the apical surface of epithelial cells that line the vertebrate gut and limits how far they may diffuse within the bilayer. The cytoskeleton is able to form appendage-like organelles, such as cilia, which are microtubule-based extensions covered by the cell membrane, and filopodia, which are actin-based extensions. These extensions are ensheathed in membrane and project from the surface of the cell in order to sense the external environment and/or make contact with the substrate or other cells. The apical surfaces of epithelial cells are dense with actin-based finger-like projections known as microvilli, which increase cell surface area and thereby increase the absorption rate of nutrients. Localized decoupling of the cytoskeleton and cell membrane results in formation of a bleb.

Cell membrane


Cell membranes contain a variety of biological molecules, notably lipids and proteins. Material is incorporated into the membrane, or deleted from it, by a variety of mechanisms: Fusion of intracellular vesicles with the membrane (exocytosis) not only excretes the contents of the vesicle but also incorporates the vesicle membrane's components into the cell membrane. The membrane may form blebs around extracellular material that pinch off to become vesicles (endocytosis). If a membrane is continuous with a tubular structure made of membrane material, then material from the tube can be drawn into the membrane continuously. Although the concentration of membrane components in the aqueous phase is low (stable membrane components have low solubility in water), there is an exchange of molecules between the lipid and aqueous phases.

The cell membrane consists of three classes of amphipathic lipids: phospholipids, glycolipids, and sterols. The amount of each depends upon the type of cell, but in the majority of cases phospholipids are the most abundant. In RBC studies, 30% of the plasma membrane is lipid. The fatty chains in phospholipids and glycolipids usually contain an even number of carbon atoms, typically between 16 and 20. The 16- and 18-carbon fatty acids are the most common. Fatty acids may be saturated or unsaturated, with the configuration of the double bonds nearly always "cis". The length and the degree of unsaturation of fatty acid chains have a profound effect on membrane fluidity as unsaturated lipids create a kink, preventing the fatty Examples of the major membrane phospholipids and glycolipids: phosphatidylcholine acids from packing together as tightly, (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), thus decreasing the melting temperature phosphatidylserine (PtdSer). (increasing the fluidity) of the membrane. The ability of some organisms to regulate the fluidity of their cell membranes by altering lipid composition is called homeoviscous adaptation. The entire membrane is held together via non-covalent interaction of hydrophobic tails, however the structure is quite fluid and not fixed rigidly in place. Under physiological conditions phospholipid molecules in the cell membrane are in the liquid crystalline state. It means the lipid molecules are free to diffuse and exhibit rapid lateral diffusion along the layer in which they are present. However, the exchange of phospholipid molecules between intracellular and extracellular leaflets of the bilayer is a very slow process. Lipid rafts and caveolae are examples of cholesterol-enriched microdomains in the cell membrane. In animal cells cholesterol is normally found dispersed in varying degrees throughout cell membranes, in the irregular spaces between the hydrophobic tails of the membrane lipids, where it confers a stiffening and

Cell membrane strengthening effect on the membrane.


Phospholipids forming lipid vesicles

Lipid vesicles or liposomes are circular pockets that are enclosed by a lipid bilayer. These structures are used in laboratories to study the effects of chemicals in cells by delivering these chemicals directly to the cell, as well as getting more insight into cell membrane permeability. Lipid vesicles and liposomes are formed by first suspending a lipid in an aqueous solution then agitating the mixture through sonication, resulting in a vesicle. By measuring the rate of efflux from that of the inside of the vesicle to the ambient solution, allows researcher to better understand membrane permeability. Vesicles can be formed with molecules and ions inside the vesicle by forming the vesicle with the desired molecule or ion present in the solution. Proteins can also be embedded into the membrane through solubilizing the desired proteins in the presence of detergents and attaching them to the phospholipids in which the liposome is formed. These provide researchers with a tool to examine various membrane protein functions.

Plasma membranes also contain carbohydrates, predominantly glycoproteins, but with some glycolipids (cerebrosides and gangliosides). For the most part, no glycosylation occurs on membranes within the cell; rather generally glycosylation occurs on the extracellular surface of the plasma membrane. The glycocalyx is an important feature in all cells, especially epithelia with microvilli. Recent data suggest the glycocalyx participates in cell adhesion, lymphocyte homing, and many others. The penultimate sugar is galactose and the terminal sugar is sialic acid, as the sugar backbone is modified in the golgi apparatus. Sialic acid carries a negative charge, providing an external barrier to charged particles.

Type Integral proteins or transmembrane proteins Description Span the membrane and have a hydrophilic cytosolic domain, which interacts with internal molecules, a hydrophobic membrane-spanning domain that anchors it within the cell membrane, and a hydrophilic extracellular domain that interacts with external molecules. The hydrophobic domain consists of one, multiple, or a combination of -helices and sheet protein motifs. Covalently bound to single or multiple lipid molecules; hydrophobically insert into the cell membrane and anchor the protein. The protein itself is not in contact with the membrane. Attached to integral membrane proteins, or associated with peripheral regions of the lipid bilayer. These proteins tend to have only temporary interactions with biological membranes, and once reacted, the molecule dissociates to carry on its work in the cytoplasm. Examples Ion channels, proton pumps, G protein-coupled receptor

Lipid anchored proteins Peripheral proteins

G proteins

Some enzymes, some hormones

The cell membrane has large content of proteins, typically around 50% of membrane volume These proteins are important for cell because they are responsible for various biological activities. Approximately a third of the genes in yeast code specifically for them, and this number is even higher in multicellular organisms. The cell membrane, being exposed to the outside environment, is an important site of cellcell communication. As such, a large variety of protein receptors and identification proteins, such as antigens, are present on the surface of the membrane. Functions of membrane proteins can also include cellcell contact, surface recognition, cytoskeleton contact, signaling, enzymatic activity, or transporting substances across the membrane. Most membrane proteins must be inserted in some way into the membrane. For this to occur, an N-terminus "signal sequence" of amino acids directs proteins to the endoplasmic reticulum, which inserts the proteins into a lipid bilayer. Once inserted, the proteins are then transported to their final destination in vesicles, where the vesicle fuses with the target membrane.

Cell membrane


The cell membrane has different lipid and protein compositions in distinct types of cells and may have therefore specific names for certain cell types: Sarcolemma in myocytes Oolemma in oocytes Axolemma in neuronal processes - axons Historically, the plasma membrane was also referred to as the plasmalemma

The permeability of a membrane is the rate of passive diffusion of molecules through the membrane. These molecules are known as permeant molecules. Permeability depends mainly on the electric charge and polarity of the molecule and to a lesser extent the molar mass of the molecule. Due to the cell membrane's hydrophobic nature, small electrically neutral molecules pass through the membrane more easily than charged, large ones. The inability of charged molecules to pass through the cell membrane results in pH partition of substances throughout the fluid compartments of the body.

Notes and references

[1] Kimball's Biology pages (http:/ / users. rcn. com/ jkimball. ma. ultranet/ BiologyPages/ C/ CellMembranes. html), Cell Membranes

External links
Lipids, Membranes and Vesicle Trafficking - The Virtual Library of Biochemistry and Cell Biology (http:// Cell membrane protein extraction protocol ( membrane extraction. htm) Membrane homeostasis, tension regulation, mechanosensitive membrane exchange and membrane traffic (http:// 3D structures of proteins associated with plasma membrane of eukaryotic cells ( localization.php?localization=Eukaryotic plasma membrane) Lipid composition and proteins of some eukariotic membranes ( php?membrane=Eukaryotic plasma membrane) ( Library resources
About Cell membrane

Resources in your library (




The cytosol is a crowded solution of many different types of molecules that fills much of the volume of cells.

Cell biology The animal cell

Components of a typical animal cell: 1. Nucleolus 2. Nucleus 3. Ribosome (little dots) 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus (or "Golgi body") 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytosol (fluid that contains organelles) 12. Lysosome 13. Centrosome 14. Cell membrane

Cytosol The cytosol or intracellular fluid (ICF) or cytoplasmic matrix is the liquid found inside cells. It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments. In the eukaryotic cell, the cytosol is within the cell membrane and is part of the cytoplasm, which also comprises the mitochondria, plastids, and other organelles (but not their internal fluids and structures); the cell nucleus is separate. In prokaryotes, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others are contained within organelles. The cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and properties within cells is not well understood. The concentrations of ions such as sodium and potassium are different in the cytosol than in the extracellular fluid; these differences in ion levels are important in processes such as osmoregulation and cell signaling. The cytosol also contains large amounts of macromolecules, which can alter how molecules behave, through macromolecular crowding. Although once thought to be a simple solution of molecules, multiple levels of organization exist in the cytosol. These include concentration gradients of small molecules such as calcium, large complexes of enzymes that act together to carry out metabolic pathways, and protein complexes such as proteasomes and carboxysomes that enclose and separate parts of the cytosol.


The term cytosol was first introduced in 1965 by H.A. Lardy, and initially referred to the liquid that was produced by breaking cells apart and pelleting all the insoluble components by ultracentrifugation. Such a soluble cell extract is not identical to the soluble part of the cell cytoplasm and is usually called a cytoplasmic fraction. The term cytosol is now used to refer to the liquid phase of the cytoplasm in an intact cell, this excludes any part of the cytoplasm that is contained within organelles. Due to the possibility of confusion between the use of the word "cytosol" to refer to both extracts of cells and the soluble part of the cytoplasm in intact cells, the phrase "aqueous cytoplasm" has been used to describe the liquid contents of the cytoplasm of living cells.

Properties and composition

The proportion of cell volume that is cytosol varies: for example while this compartment forms the bulk of cell structure in bacteria, in plant cells the main compartment is the large central vacuole. The cytosol consists mostly of water, dissolved ions, small molecules, and large water-soluble molecules (such as proteins). The majority of these non-protein molecules have a molecular mass of less than 300Da. This mixture of small molecules is extraordinarily complex, as the variety of molecules that are involved in metabolism (the metabolites) is immense. For example up to 200,000 different small molecules might be made in plants, although not all these will be present in the same species, or in a single cell. Indeed, estimates of the number of metabolites in single cells such as E. coli and baker's yeast predict that under 1,000 are made.

Most of the cytosol is water, which makes up about 70% of the total volume of a typical cell. The pH of the intracellular fluid is 7.4. while human cytosolic pH ranges between 7.0 - 7.4, and is usually higher if a cell is growing. The viscosity of cytoplasm is roughly the same as pure water, although diffusion of small molecules through this liquid is about fourfold slower than in pure water, due mostly to collisions with the large numbers of macromolecules in the cytosol. Studies in the brine shrimp have examined how water affects cell functions; these saw that a 20% reduction in the amount of water in a cell inhibits metabolism, with metabolism decreasing progressively as the cell dries out and all metabolic activity halting when the water level reaches 70% below normal.

Cytosol Although water is vital for life, the structure of this water in the cytosol is not well understood, mostly because methods such as nuclear magnetic resonance only give information on the average structure of water, and cannot measure local variations at the microscopic scale. Even the structure of pure water is poorly understood, due to the ability of water to form structures such as water clusters through hydrogen bonds. The classic view of water in cells is that about 5% of this water is strongly bound in by solutes or macromolecules as water of solvation, while the majority has the same structure as pure water. This water of solvation is not active in osmosis and may have different solvent properties, so that some dissolved molecules are excluded, while others become concentrated. However, others argue that the effects of the high concentrations of macromolecules in cells extend throughout the cytosol and that water in cells behaves very differently from the water in dilute solutions. These ideas include the proposal that cells contain zones of low and high-density water, which could have widespread effects on the structures and functions of the other parts of the cell. However, the use of advanced nuclear magnetic resonance methods to directly measure the mobility of water in living cells contradicts this idea, as it suggests that 85% of cell water acts like that pure water, while the remainder is less mobile and probably bound to macromolecules.


The concentrations of the other ions in cytosol are quite different from those in extracellular fluid and the cytosol also contains much higher amounts of charged macromolecules such as proteins and nucleic acids than the outside of the cell.

Typical ion concentrations in mammalian cytosol and blood.

Ion Potassium Sodium Chloride Bicarbonate Amino acids in proteins Magnesium Calcium Concentration in cytosol (millimolar) Concentration in blood (millimolar) 139 12 4 12 138 0.8 <0.0002 4 145 116 29 9 1.5 1.8

In contrast to extracellular fluid, cytosol has a high concentration of potassium ions and a low concentration of sodium ions. This difference in ion concentrations is critical for osmoregulation, since if the ion levels were the same inside a cell as outside, water would enter constantly by osmosis - since the levels of macromolecules inside cells are higher than their levels outside. Instead, sodium ions are expelled and potassium ions taken up by the Na/K-ATPase, potassium ions then flow down their concentration gradient through potassium-selection ion channels, this loss of positive charge creates a negative membrane potential. To balance this potential difference, negative chloride ions also exit the cell, through selective chloride channels. The loss of sodium and chloride ions compensates for the osmotic effect of the higher concentration of organic molecules inside the cell. Cells can deal with even larger osmotic changes by accumulating osmoprotectants such as betaines or trehalose in their cytosol. Some of these molecules can allow cells to survive being completely dried out and allow an organism to enter a state of suspended animation called cryptobiosis. In this state the cytosol and osmoprotectants become a glass-like solid that helps stabilize proteins and cell membranes from the damaging effects of desiccation. The low concentration of calcium in the cytosol allows calcium ions to function as a second messenger in calcium signaling. Here, a signal such as a hormone or an action potential opens calcium channels so that calcium floods into the cytosol. This sudden increase in cytosolic calcium activates other signalling molecules, such as calmodulin and

Cytosol protein kinase C. Other ions such as chloride and potassium may also have signaling functions in the cytosol, but these are not well understood.


Protein molecules that do not bind to cell membranes or the cytoskeleton are dissolved in the cytosol. The amount of protein in cells is extremely high, and approaches 200mg/ml, occupying about 20-30% of the volume of the cytosol. However, measuring precisely how much protein is dissolved in cytosol in intact cells is difficult, since some proteins appear to be weakly associated with membranes or organelles in whole cells and are released into solution upon cell lysis. Indeed, in experiments where the plasma membrane of cells were carefully disrupted using saponin, without damaging the other cell membranes, only about one quarter of cell protein was released. These cells were also able to synthesize proteins if given ATP and amino acids, implying that many of the enzymes in cytosol are bound to the cytoskeleton. However, the idea that the majority of the proteins in cells are tightly bound in a network called the microtrabecular lattice is now seen as unlikely. In prokaryotes the cytosol contains the cell's genome, within a structure known as a nucleoid. This is an irregular mass of DNA and associated proteins that control the transcription and replication of the bacterial chromosome and plasmids. In eukaryotes the genome is held within the cell nucleus, which is separated from the cytosol by nuclear pores that block the free diffusion of any molecule larger than about 10nanometres in diameter. This high concentration of macromolecules in cytosol causes an effect called macromolecular crowding, which is when the effective concentration of other macromolecules is increased, since they have less volume to move in. This crowding effect can produce large changes in both the rates and the position of chemical equilibrium of reactions in the cytosol. It is particularly important in its ability to alter dissociation constants by favoring the association of macromolecules, such as when multiple proteins come together to form protein complexes, or when DNA-binding proteins bind to their targets in the genome.

Although the components of the cytosol are not separated into regions by cell membranes, these components do not always mix randomly and several levels of organization can localize specific molecules to defined sites within the cytosol.

Concentration gradients
Although small molecules diffuse rapidly in the cytosol, concentration gradients can still be produced within this compartment. A well-studied example of these are the "calcium sparks" that are produced for a short period in the region around an open calcium channel. These are about 2micrometres in diameter and last for only a few milliseconds, although several sparks can merge to form larger gradients, called "calcium waves". Concentration gradients of other small molecules, such as oxygen and adenosine triphosphate may be produced in cells around clusters of mitochondria, although these are less well understood.

Protein complexes
Proteins can associate to form protein complexes, these often contain a set of proteins with similar functions, such as enzymes that carry out several steps in the same metabolic pathway. This organization can allow substrate channeling, which is when the product of one enzyme is passed directly to the next enzyme in a pathway without being released into solution. Channeling can make a pathway more rapid and efficient than it would be if the enzymes were randomly distributed in the cytosol, and can also prevent the release of unstable reaction intermediates. Although a wide variety of metabolic pathways involve enzymes that are tightly bound to each other, others may involve more loosely associated complexes that are very difficult to study outside the cell. Consequently, the importance of these complexes for metabolism in general remains unclear.



Protein compartments
Some protein complexes contain a large central cavity that is isolated from the remainder of the cytosol. One example of such an enclosed compartment is the proteasome. Here, a set of subunits form a hollow barrel containing proteases that degrade Carboxysomes are protein-enclosed bacterial microcompartments within the cytosol. On cytosolic proteins. Since these would the left is an electron microscope image of carboxysomes, and on the right a model of their structure. be damaging if they mixed freely with the remainder of the cytosol, the barrel is capped by a set of regulatory proteins that recognize proteins with a signal directing them for degradation (a ubiquitin tag) and feed them into the proteolytic cavity. Another large class of protein compartments are bacterial microcompartments, which are made of a protein shell that encapsulates various enzymes. These compartments are typically about 100-200 nanometres across and made of interlocking proteins. A well-understood example is the carboxysome, which contains enzymes involved in carbon fixation such as RuBisCO.

Cytoskeletal sieving
Although the cytoskeleton is not part of the cytosol, the presence of this network of filaments restricts the diffusion of large particles in the cell. For example, in several studies tracer particles larger than about 25nanometres (about the size of a ribosome) were excluded from parts of the cytosol around the edges of the cell and next to the nucleus. These "excluding compartments" may contain a much denser meshwork of actin fibres than the remainder of the cytosol. These microdomains could influence the distribution of large structures such as ribosomes and organelles within the cytosol by excluding them from some areas and concentrating them in others.

The cytosol has no single function and is instead the site of multiple cell processes. Examples of these processes include signal transduction from the cell membrane to sites within the cell, such as the cell nucleus, or organelles. This compartment is also the site of many of the processes of cytokinesis, after the breakdown of the nuclear membrane in mitosis. Another major function of cytosol is to transport metabolites from their site of production to where they are used. This is relatively simple for water-soluble molecules, such as amino acids, which can diffuse rapidly through the cytosol. However, hydrophobic molecules, such as fatty acids or sterols, can be transported through the cytosol by specific binding proteins, which shuttle these molecules between cell membranes. Molecules taken into the cell by endocytosis or on their way to be secreted can also be transported through the cytosol inside vesicles, which are small spheres of lipids that are moved along the cytoskeleton by motor proteins. The cytosol is the site of most metabolism in prokaryotes, and a large proportion of the metabolism of eukaryotes. For instance, in mammals about half of the proteins in the cell are localized to the cytosol. The most complete data are available in yeast, where metabolic reconstructions indicate that the majority of both metabolic processes and metabolites occur in the cytosol. Major metabolic pathways that occur in the cytosol in animals are protein biosynthesis, the pentose phosphate pathway, glycolysis and gluconeogenesis. The localization of pathways can be different in other organisms, for instance fatty acid synthesis occurs in chloroplasts in plants and in apicoplasts in apicomplexa.



References Further reading

Wheatley, Denys N.; Pollack, Gerald H.; Cameron, Ivan L. (2006). Water and the Cell. Berlin: Springer. ISBN1-4020-4926-9. OCLC 71298997 (



Cell biology The animal cell

Components of a typical animal cell: 1. Nucleolus 2. Nucleus 3. Ribosome (little dots) 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus (or "Golgi body") 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytosol (fluid that contains organelles) 12. Lysosome 13. Centrosome 14. Cell membrane

The cytoplasm comprises cytosol the gel-like substance enclosed within the cell membrane and the organelles the cell's internal sub-structures. All of the contents of the cells of prokaryote organisms (such as bacteria, which lack a cell nucleus) are contained within the cytoplasm. Within the cells of eukaryote organisms the contents of the cell nucleus are separated from the cytoplasm, and are then called the nucleoplasm. The cytoplasm is about 80% water and usually colorless. It is within the cytoplasm that most cellular activities occur, such as many metabolic pathways including glycolysis, and processes such as cell division. The inner, granular mass is called the endoplasm and the outer, clear and glassy layer is called the cell cortex or the ectoplasm. Movement of calcium ions in and out of the cytoplasm is thought to be a signaling activity for metabolic processes.[1] In plants, movements of the cytoplasm around vacuoles are known as cytoplasmic streaming.



The cytoplasm has three major elements; the cytosol, organelles and inclusions.

The cytosol is the portion of the cytoplasm not contained within membrane-bound organelles. Cytosol makes up about 70% of the cell volume and is composed of water, salts and organic molecules.[2] The cytosol is a complex mixture of cytoskeleton filaments, dissolved molecules, and water that fills much of the volume of a cell. The cytosol also contains the protein filaments that make up the cytoskeleton, as well as soluble proteins and small structures such as ribosomes, proteasomes, and the mysterious vault complexes. The inner, granular and more fluid portion of the cytoplasm is referred to as endoplasm. Due to this network of fibres and high concentrations of dissolved macromolecules, such as proteins, an effect called macromolecular crowding occurs and the cytosol does not act as an ideal solution. This crowding effect alters how the components of the cytosol interact with each other.

Organelles (literally "little organs"), are usually membrane-bound, and are structures inside the cell that have specific functions. Some major organelles that are suspended in the cytosol are the mitochondria, the endoplasmic reticulum, the Golgi apparatus, vacuoles, lysosomes, and in plant cells chloroplasts.

Cytoplasmic inclusions
The inclusions are small particles of insoluble substances suspended in the cytosol. A huge range of inclusions exist in different cell types, and range from Proteins in different cellular compartments and structures tagged crystals of calcium oxalate or silicon dioxide in plants, with green fluorescent protein to granules of energy-storage materials such as starch, glycogen, or polyhydroxybutyrate. A particularly widespread example are lipid droplets, which are spherical droplets composed of lipids and proteins that are used in both prokaryotes and eukaryotes as a way of storing lipids such as fatty acids and sterols. Lipid droplets make up much of the volume of adipocytes, which are specialized lipid-storage cells, but they are also found in a range of other cell types.

Controversy and research

The cytoplasm, mitochondria and most organelles are contributions to the cell from the maternal gamete. There is considerably less research and understanding on cytoplasmic inheritance/maternal inheritance and mitochondrial DNA compared to the cell nucleus and genomic DNA. Historically, there has been neglect of researching whatever has been labeled female or feminine. The cytoplasm is one organelle that has been labeled feminine. The cytoplasm/nucleus being labeled as feminine/masculine follows the example of egg/sperm being gendered; both cytoplasm and egg are considered nonresistant to the efforts and pursuits of the active nucleus and sperm. The "passivity of the egg becomes the passivity of the cytoplasm." Contrary to the older information that disregards any

Cytoplasm notion of the cytoplasm being active, new research has shown it to be in control of movement and flow of nutrients in and out of the cell by "viscoplastic behavior and... a measure of the reciprocal rate of bond breakadge within the cytoplasmic network."


[1] C. Michael Hogan. 2010. Calcium. eds. A.Jorgensen, C. Cleveland. Encyclopedia of Earth (http:/ / www. eoearth. org/ article/ Calcium?topic=49557). National Council for Science and the Environment. [2] Cytoplasm Composition (http:/ / web. archive. org/ web/ 20070331230518/ http:/ / sun. menloschool. org/ ~birchler/ cells/ animals/ cytoplasm/ ).

External links
Luby-Phelps K (2000). "Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area" ( pdf) (PDF). Int Rev Cytol. International Review of Cytology 192: 189221. doi: 10.1016/S0074-7696(08)60527-6 ( ISBN9780123645968. PMID 10553280 (http://www.

Latin organella Code TH H1. [1]

Cell biology The animal cell



Components of a typical animal cell: 1. Nucleolus 2. Nucleus 3. Ribosome (little dots) 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus (or "Golgi body") 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytosol (fluid that contains organelles) 12. Lysosome 13. Centrosome 14. Cell membrane

In cell biology, an organelle /rnl/ is a specialized subunit within a cell that has a specific function, and it is usually separately enclosed within its own lipid bilayer. The name organelle comes from the idea that these structures are to cells what an organ is to the body (hence the name organelle, the suffix -elle being a diminutive). Organelles are identified by microscopy, and can also be purified by cell fractionation. There are many types of organelles, particularly in eukaryotic cells. While prokaryotes do not possess organelles per se, some do contain protein-based microcompartments, which are thought to act as primitive organelles.

History and terminology

In biology organs are defined as confined functional units within an organism. The analogy of bodily organs to microscopic cellular substructures is obvious, as from even early works, authors of respective textbooks rarely elaborate on the distinction between the two. Credited as the first[2][3] to use a diminutive of organ (i.e., little organ) for cellular structures was German zoologist Karl August Mbius (1884), who used the term organula (plural of organulum, the diminutive of Latin organum). From the context, it is clear that he referred to reproduction related structures of protists. In a footnote, which was published as a correction in the next issue of the journal, he justified his suggestion to call organs of unicellular organisms "organella" since they are only differently formed parts of one cell, in contrast to multicellular organs of multicellular organisms. Thus, the original definition was limited to structures of unicellular organisms. It would take several years before organulum, or the later term organelle, became accepted and expanded in meaning to include subcellular structures in multicellular organisms. Books around 1900 from Valentin Hcker, Edmund Wilson and Oscar Hertwig still referred to cellular organs. Later, both terms came to be used side by side: Bengt Lidforss wrote 1915 (in German) about "Organs or Organells".

Organelle Around 1920, the term organelle was used to describe propulsion structures ("motor organelle complex", i.e., flagella and their anchoring) and other protist structures, such as ciliates.[4] Alfred Khn wrote about centrioles as division organelles, although he stated that, for Vahlkampfias, the alternative 'organelle' or 'product of structural build-up' had not yet been decided, without explaining the difference between the alternatives. In his 1953 textbook, Max Hartmann used the term for extracellular (pellicula, shells, cell walls) and intracellular skeletons of protists. Later, the now widely used[5][6][7][8] definition of organelle emerged, after which only cellular structures with surrounding membrane had been considered organelles. However, the more original definition of subcellular functional unit in general still coexists.[9] In 1978, Albert Frey-Wyssling suggested that the term organelle should refer only to structures that convert energy, such as centrosomes, ribosomes, and nucleoli. This new definition, however, did not win wide recognition.


Types of organelles
While most cell biologists consider the term organelle to be synonymous with "cell compartment", other cell biologists choose to limit the term organelle to include only those that are DNA-containing, having originated from formerly autonomous microscopic organisms acquired via endosymbiosis. Under this definition, there would only be two broad classes of organelles (i.e. those that contain their own DNA, and have originated from endosymbiotic bacteria): mitochondria (in almost all eukaryotes) plastids[10] (e.g. in plants, algae, and some protists). Other organelles are also suggested to have endosymbiotic origins, but do not contain their own DNA (notably the flagellum see evolution of flagella). Under the more restricted definition of membrane-bound structures, some parts of the cell do not qualify as organelles. Nevertheless, the use of organelle to refer to non-membrane bound structures such as ribosomes is common.[11] This has led some texts to delineate between membrane-bound and non-membrane bound organelles.[12] These structures are large assemblies of macromolecules that carry out particular and specialized functions, but they lack membrane boundaries. Such cell structures include: large RNA and protein complexes: ribosome, spliceosome, vault large protein complexes: proteasome, DNA polymerase III holoenzyme, RNA polymerase II holoenzyme, symmetric viral capsids, complex of GroEL and GroES; membrane protein complexes: photosystem I, ATP synthase large DNA and protein complexes: nucleosome centriole and microtubule-organizing center (MTOC) cytoskeleton flagellum cellular structure which is not membrane bound and does not have a well-defined structure: nucleolus



Eukaryotic organelles
Eukaryotic cells are structurally complex, and by definition are organized, in part, by interior compartments that are themselves enclosed by lipid membranes that resemble the outermost cell membrane. The larger organelles, such as the nucleus and vacuoles, are easily visible with the light microscope. They were among the first biological discoveries made after the invention of the microscope. Not all eukaryotic cells have each of the organelles listed below. Exceptional organisms have cells that do not include some organelles that might otherwise be considered universal to eukaryotes (such as mitochondria). There are also occasional exceptions to the number of membranes surrounding organelles, listed in the tables below (e.g., some that are listed as double-membrane are sometimes found with single or triple membranes). In addition, the number of individual organelles of each type found in a given cell varies depending upon the function of that cell.

Major eukaryotic organelles

Organelle chloroplast (plastid) Main function photosynthesis, traps energy from sunlight Structure double-membrane compartment Organisms plants, protists (rare kleptoplastic organisms) all eukaryotes Notes has some genes; theorized to be engulfed by the ancestral eukaryotic cell (endosymbiosis) rough endoplasmic reticulum is covered with ribosomes, has folds that are flat sacs; smooth endoplasmic reticulum has folds that are tubular cis-face (convex) nearest to rough endoplasmic reticulum; trans-face (concave) farthest from rough endoplasmic reticulum has some DNA; theorized to be engulfed by an ancestral eukaryotic cell (endosymbiosis)

endoplasmic reticulum

translation and folding of new proteins single-membrane (rough endoplasmic reticulum), expression compartment of lipids (smooth endoplasmic reticulum)

Golgi apparatus

sorting, packaging, processing and modification of proteins

single-membrane compartment

all eukaryotes


energy production from the oxidation of glucose substances and the release of adenosine triphosphate storage,transportation, helps maintain homeostasis DNA maintenance, controls all activities of the cell, RNA transcription

double-membrane compartment

most eukaryotes


single-membrane compartment double-membrane compartment



all eukaryotes

contains bulk of genome

Mitochondria and chloroplasts, which have double-membranes and their own DNA, are believed to have originated from incompletely consumed or invading prokaryotic organisms, which were adopted as a part of the invaded cell. This idea is supported in the Endosymbiotic theory.

Minor eukaryotic organelles and cell components

Organelle/Macromolecule acrosome Main function helps spermatozoa fuse with ovum Structure single-membrane compartment double-membrane compartment Microtubule protein many animals Organisms


vesicle that sequesters cytoplasmic material and organelles for degradation anchor for cytoskeleton, organizes cell division by forming spindle fibers movement in or of external medium; "critical developmental signaling pathway".

all eukaryotes




Microtubule protein

animals, protists, few plants


detects light, allowing phototaxis to take place green algae and other unicellular photosynthetic organisms such as euglenids single-membrane compartment single-membrane compartment double-membrane compartment single-membrane compartment single-membrane compartment Some protozoa, such as Trypanosomes.

eyespot apparatus


carries out glycolysis


conversion of fat into sugars



energy & hydrogen production

a few unicellular eukaryotes


breakdown of large molecules (e.g., proteins + polysaccharides) pigment storage

most eukaryotes




probably plays a role in Fe-S cluster assembly double-membrane compartment myocyte contraction pre-ribosome production not characterized breakdown of metabolic hydrogen peroxide bundled filaments protein-DNA-RNA not characterized single-membrane compartment very large protein complex RNA-protein single-membrane compartment

a few unicellular eukaryotes that lack mitochondria animals most eukaryotes fungi all eukaryotes

myofibril nucleolus parenthesome peroxisome


degradation of unneeded or damaged proteins by proteolysis translation of RNA into proteins material transport

All eukaryotes, all archaea, some bacteria

ribosome (80S) vesicle

all eukaryotes all eukaryotes

Other related structures: cytosol endomembrane system nucleosome microtubule cell membrane

Prokaryotic organelles
Prokaryotes are not as structurally complex as eukaryotes, and were once thought not to have any internal structures enclosed by lipid membranes. In the past, they were often viewed as having little internal organization; but, slowly, details are (A) Electron micrograph of Halothiobacillus neapolitanus cells, arrows highlight carboxysomes. (B) Image of intact carboxysomes isolated from H. neapolitanus. Scale emerging about prokaryotic internal bars are 100 nm. structures. An early false turn was the idea developed in the 1970s that bacteria might contain membrane folds termed mesosomes, but these were later shown to be artifacts produced by the chemicals used to prepare the cells for electron microscopy.

Organelle However, more recent research has revealed that at least some prokaryotes have microcompartments such as carboxysomes. These subcellular compartments are 100200nm in diameter and are enclosed by a shell of proteins. Even more striking is the description of membrane-bound magnetosomes in bacteria, as well as the nucleus-like structures of the Planctomycetes that are surrounded by lipid membranes.


Prokaryotic organelles and cell components

Organelle/Macromolecule carboxysome chlorosome flagellum magnetosome nucleoid Main function carbon fixation photosynthesis movement in external medium magnetic orientation Structure protein-shell compartment light harvesting complex protein filament inorganic crystal, lipid membrane Organisms some bacteria green sulfur bacteria some prokaryotes and eukaryotes magnetotactic bacteria prokaryotes

DNA maintenance, transcription to DNA-protein RNA DNA exchange translation of RNA into proteins photosynthesis circular DNA RNA-protein photosystem proteins and pigments

plasmid ribosome (70S) thylakoid mesosomes

some bacteria bacteria and archaea mostly cyanobacteria present in most of the prokaryotic cells

functions of golgi bodies,centrioles small irregular shaped oraganelle containing etc.. ribosomes

Proteins and organelles

The function of a protein is closely correlated with the organelle in which it resides. Some methods were proposed for predicting the organelle in which an uncharacterized protein is located according to its amino acid composition and some methods were based on pseudo amino acid composition.

[1] http:/ / www. unifr. ch/ ifaa/ Public/ EntryPage/ ViewTH/ THh100. html [2] Amer. Naturalist. 23, 1889, p. 183: "It may possibly be of advantage to use the word organula here instead of organ, following a suggestion by Mbius. Functionally differentiated multicellular aggregates in multicellular forms or metazoa are in this sense organs, while, for functionally differentiated portions of unicellular organisms or for such differentiated portions of the unicellular germ-elements of metazoa, the diminutive organula is appropriate." Cited after: Oxford English Dictionary online, entry for "organelle". [3] 'Journal de l'anatomie et de la physiologie normales et pathologiques de l'homme et des animaux' at Google Books (http:/ / books. google. com/ books?id=yAQwAAAAIAAJ& q=Organulum+ OR+ Organula+ OR+ Organella+ date:1800-1900& dq=Organulum+ OR+ Organula+ OR+ Organella+ date:1800-1900& as_brr=0& pgis=1) [4] Cl. Hamburger, Handwrterbuch der Naturw. Bd. V,. p. 435. Infusorien. cited after [5] Nultsch, Allgemeine Botanik, 11. Aufl. 2001, Thieme Verlag [6] Wehner/Gehring, Zoologies, 23. Aufl. 1995, Thieme Verlag [7] Alberts, Bruce et al. (2002). The Molecular Biology of the Cell, 4th ed., Garland Science, 2002, ISBN 0-8153-3218-1. online via "NCBI-Bookshelf" (http:/ / www. ncbi. nlm. nih. gov/ entrez/ query. fcgi?db=Books& itool=toolbar) [8] Brock, Mikrobiologie, 2. korrigierter Nachdruck (2003), der 1. Aufl. von 2001 [9] Strasburgers Lehrbuch der Botanik fr Hochschulen, 35. Aufl. (2002), p. 42 [10] C.Michael Hogan. 2010. Deoxyribonucleic acid. Encyclopedia of Earth. National Council for Science and the Environment. (http:/ / www. eoearth. org/ articles/ view/ 158858/ ?topic=49496) S. Draggan and C. Cleveland (eds.). Washington DC [11] Campbell and Reece, Biology 6th edition, Benjamin Cummings, 2002 [12] Cormack, David H. (1984) Introduction to Histology, Lippincott, ISBN 0397521146



External links
Tree of Life Eukaryotes ( Library resources
About Organelle

Resources in your library (

Cell nucleus
Cell biology The animal cell

Components of a typical animal cell: 1. Nucleolus 2. Nucleus 3. Ribosome (little dots) 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus (or "Golgi body") 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytosol (fluid that contains organelles) 12. Lysosome 13. Centrosome 14. Cell membrane

In cell biology, the nucleus (pl. nuclei; from Latin nucleus or nuculeus, meaning kernel) is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these chromosomes are the cell's nuclear genome. The function of the nucleus is to maintain the integrity of these genes and to control the activities of the cell by regulating gene expression the nucleus is, therefore, the control center of the cell. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm, and the nucleoskeleton (which includes nuclear lamina), a network within the nucleus that adds mechanical support, much like the cytoskeleton, which supports the cell as a whole. Movement of large molecules such as proteins and RNA through the pores is required for both gene expression and the maintenance of chromosomes. Because the nuclear membrane is

Cell nucleus impermeable to large molecules, nuclear pores are required that regulate nuclear transport of molecules across the envelope. The pores cross both nuclear membranes, providing a channel through which larger molecules must be actively transported by carrier proteins while allowing free movement of small molecules and ions. The interior of the nucleus does not contain any membrane-bound sub compartments, its contents are not uniform, and a number of sub-nuclear bodies exist, made up of unique proteins, RNA molecules, and particular parts of the chromosomes. The best-known of these is the nucleolus, which is mainly involved in the assembly of ribosomes. After being produced in the nucleolus, ribosomes are exported to the cytoplasm where they translate mRNA.


The nucleus was the first organelle to be discovered. What is most likely the oldest preserved drawing dates back to the early microscopist Antonie van Leeuwenhoek (1632 1723). He observed a "Lumen", the nucleus, in the red blood cells of salmon.[1] Unlike mammalian red blood cells, those of other vertebrates still Oldest known depiction of cells and their nuclei by Antonie van Leeuwenhoek, 1719. possess nuclei. The nucleus was also described by Franz Bauer in 1804 and in more detail in 1831 by Scottish botanist Robert Brown in a talk at the Linnean Society of London. Brown was studying orchids under microscope when he observed an opaque area, which he called the areola or nucleus, in the cells of the flower's outer layer. He did not suggest a potential function. In 1838, Matthias Schleiden proposed that the nucleus plays a role in generating cells, thus he introduced the name "Cytoblast" (cell builder). He believed that he had observed new cells assembling around "cytoblasts". Franz Meyen was a strong opponent of this view, having already described cells Drawing of a Chironomus salivary gland cell multiplying by division and believing that many published by Walther Flemming in 1882. The cells would have no nuclei. The idea that cells can nucleus contains Polytene chromosomes. be generated de novo, by the "cytoblast" or otherwise, contradicted work by Robert Remak (1852) and Rudolf Virchow (1855) who decisively propagated the new paradigm that cells are generated solely by cells ("Omnis cellula e cellula"). The function of the nucleus remained unclear.[2] Between 1877 and 1878, Oscar Hertwig published several studies on the fertilization of sea urchin eggs, showing that the nucleus of the sperm enters the oocyte and fuses with its nucleus. This was the first time it was suggested that an individual develops from a (single) nucleated cell. This was in contradiction to Ernst Haeckel's theory that the complete phylogeny of a species would be repeated during embryonic development, including generation of the first nucleated cell from a "Monerula", a structureless mass of primordial mucus ("Urschleim"). Therefore, the necessity of the sperm nucleus for fertilization was discussed for quite some time. However, Hertwig confirmed his observation in other animal groups, e.g., amphibians and molluscs. Eduard Strasburger produced the same results for plants (1884). This paved the way to assign the nucleus an important role in heredity. In 1873, August Weismann

Cell nucleus postulated the equivalence of the maternal and paternal germ cells for heredity. The function of the nucleus as carrier of genetic information became clear only later, after mitosis was discovered and the Mendelian rules were rediscovered at the beginning of the 20th century; the chromosome theory of heredity was therefore developed.


The nucleus is the largest cellular organelle in animals. In mammalian cells, the average diameter of the nucleus is approximately 6 micrometers (m), which occupies about 10% of the total cell volume. The viscous liquid within it is called nucleoplasm, and is similar in composition to the cytosol found outside the nucleus. It appears as a dense, roughly spherical organelle.

Nuclear envelope and pores

The eukaryotic cell nucleus. Visible in this diagram are the ribosome-studded double membranes of the nuclear envelope, the DNA (complexed as chromatin), and the nucleolus. Within the cell nucleus is a viscous liquid called nucleoplasm, similar to the cytoplasm found outside the nucleus.

A cross section of a nuclear pore on the surface of the nuclear envelope (1). Other diagram labels show (2) the outer ring, (3) spokes, (4) basket, and (5) filaments.

The nuclear envelope, otherwise known as nuclear membrane, consists of two cellular membranes, an inner and an outer membrane, arranged parallel to one another and separated by 10 to 50 nanometers (nm). The nuclear envelope completely encloses the nucleus and separates the cell's genetic material from the surrounding cytoplasm, serving as a barrier to prevent macromolecules from diffusing freely between the nucleoplasm and the cytoplasm. The outer nuclear membrane is continuous with the membrane of the rough endoplasmic reticulum (RER), and is similarly studded with ribosomes. The space between the membranes is called the perinuclear space and is continuous with the RER lumen. Nuclear pores, which provide aqueous channels through the envelope, are composed of multiple proteins, collectively referred to as nucleoporins. The pores are about 125 million daltons in molecular weight and consist of around 50 (in yeast) to several hundred proteins (in vertebrates). The pores are 100nm in total diameter; however, the gap through which molecules freely diffuse is only about 9nm wide, due to the presence of regulatory systems within the center of the pore. This size selectively allows the passage of small water-soluble molecules while preventing larger molecules, such as nucleic acids and larger proteins, from inappropriately entering or exiting the nucleus. These large molecules must be actively transported into the nucleus instead. The nucleus of a typical mammalian cell will have about 3000 to 4000 pores throughout its envelope, each of which contains an eightfold-symmetric ring-shaped structure at a position where the inner and outer membranes fuse. Attached to the

Cell nucleus ring is a structure called the nuclear basket that extends into the nucleoplasm, and a series of filamentous extensions that reach into the cytoplasm. Both structures serve to mediate binding to nuclear transport proteins. Most proteins, ribosomal subunits, and some DNAs are transported through the pore complexes in a process mediated by a family of transport factors known as karyopherins. Those karyopherins that mediate movement into the nucleus are also called importins, whereas those that mediate movement out of the nucleus are called exportins. Most karyopherins interact directly with their cargo, although some use adaptor proteins. Steroid hormones such as cortisol and aldosterone, as well as other small lipid-soluble molecules involved in intercellular signaling, can diffuse through the cell membrane and into the cytoplasm, where they bind nuclear receptor proteins that are trafficked into the nucleus. There they serve as transcription factors when bound to their ligand; in the absence of ligand, many such receptors function as histone deacetylases that repress gene expression.


Nuclear lamina
In animal cells, two networks of intermediate filaments provide the nucleus with mechanical support: The nuclear lamina forms an organized meshwork on the internal face of the envelope, while less organized support is provided on the cytosolic face of the envelope. Both systems provide structural support for the nuclear envelope and anchoring sites for chromosomes and nuclear pores. The nuclear lamina is composed mostly of lamin proteins. Like all proteins, lamins are synthesized in the cytoplasm and later transported to the nucleus interior, where they are assembled before being incorporated into the existing network of nuclear lamina. Lamins found on the cytosolic face of the membrane, such as emerin and nesprin, bind to the cytoskeleton to provide structural support. Lamins are also found inside the nucleoplasm where they form another regular structure, known as the nucleoplasmic veil, that is visible using fluorescence microscopy. The actual function of the veil is not clear, although it is excluded from the nucleolus and is present during interphase. Lamin structures that make up the veil, such as LEM3, bind chromatin and disrupting their structure inhibits transcription of protein-coding genes. Like the components of other intermediate filaments, the lamin monomer contains an alpha-helical domain used by two monomers to coil around each other, forming a dimer structure called a coiled coil. Two of these dimer structures then join side by side, in an antiparallel arrangement, to form a tetramer called a protofilament. Eight of these protofilaments form a lateral arrangement that is twisted to form a ropelike filament. These filaments can be assembled or disassembled in a dynamic manner, meaning that changes in the length of the filament depend on the competing rates of filament addition and removal. Mutations in lamin genes leading to defects in filament assembly are known as laminopathies. The most notable laminopathy is the family of diseases known as progeria, which causes the appearance of premature aging in its sufferers. The exact mechanism by which the associated biochemical changes give rise to the aged phenotype is not well understood.

Cell nucleus


The cell nucleus contains the majority of the cell's genetic material in the form of multiple linear DNA molecules organized into structures called chromosomes. Each human cell contains roughly two meters of DNA. During most of the cell cycle these are organized in a DNA-protein complex known as chromatin, and during cell division the chromatin can be seen to form the well-defined chromosomes familiar from a karyotype. A small fraction of the cell's genes are located instead in the mitochondria. There are two types of chromatin. Euchromatin is the less compact DNA form, and contains genes that are frequently expressed by the cell. The other type, heterochromatin, is the more compact form, and contains DNA that is infrequently transcribed. This structure is further categorized into facultative heterochromatin, A mouse fibroblast nucleus in which DNA is stained blue. The distinct chromosome territories of consisting of genes that are organized as heterochromatin only in chromosome 2 (red) and chromosome 9 (green) are certain cell types or at certain stages of development, and stained with fluorescent in situ hybridization. constitutive heterochromatin that consists of chromosome structural components such as telomeres and centromeres. During interphase the chromatin organizes itself into discrete individual patches, called chromosome territories. Active genes, which are generally found in the euchromatic region of the chromosome, tend to be located towards the chromosome's territory boundary. Antibodies to certain types of chromatin organization, in particular, nucleosomes, have been associated with a number of autoimmune diseases, such as systemic lupus erythematosus. These are known as anti-nuclear antibodies (ANA) and have also been observed in concert with multiple sclerosis as part of general immune system dysfunction. As in the case of progeria, the role played by the antibodies in inducing the symptoms of autoimmune diseases is not obvious.

The nucleolus is a discrete densely stained structure found in the nucleus. It is not surrounded by a membrane, and is sometimes called a suborganelle. It forms around tandem repeats of rDNA, DNA coding for ribosomal RNA (rRNA). These regions are called nucleolar organizer regions (NOR). The main roles of the nucleolus are to synthesize rRNA and assemble ribosomes. The structural cohesion of the nucleolus depends on its activity, as ribosomal assembly in the nucleolus results in the transient association of nucleolar components, facilitating further ribosomal assembly, and hence further association. This model is supported by observations that inactivation of rDNA results in intermingling of nucleolar structures.
An electron micrograph of a cell nucleus, showing the darkly stained nucleolus.

In the first step of ribosome assembly, a protein called RNA polymerase I transcribes rDNA, which forms a large pre-rRNA precursor. This is cleaved into the subunits 5.8S, 18S, and 28S

Cell nucleus


rRNA. The transcription, post-transcriptional processing, and assembly of rRNA occurs in the nucleolus, aided by small nucleolar RNA (snoRNA) molecules, some of which are derived from spliced introns from messenger RNAs encoding genes related to ribosomal function. The assembled ribosomal subunits are the largest structures passed through the nuclear pores. When observed under the electron microscope, the nucleolus can be seen to consist of three distinguishable regions: the innermost fibrillar centers (FCs), surrounded by the dense fibrillar component (DFC), which in turn is bordered by the granular component (GC). Transcription of the rDNA occurs either in the FC or at the FC-DFC boundary, and, therefore, when rDNA transcription in the cell is increased, more FCs are detected. Most of the cleavage and modification of rRNAs occurs in the DFC, while the latter steps involving protein assembly onto the ribosomal subunits occur in the GC.

3D rendering of nucleus with location of nucleolus

Other subnuclear bodies

Structure name Structure diameter Cajal bodies PIKA PML bodies Paraspeckles Speckles 0.22.0m 5m 0.21.0m 0.21.0m 2025nm

|+ Subnuclear structure sizes Besides the nucleolus, the nucleus contains a number of other non-membrane-delineated bodies. These include Cajal bodies, Gemini of coiled bodies, polymorphic interphase karyosomal association (PIKA), promyelocytic leukaemia (PML) bodies, paraspeckles, and splicing speckles. Although little is known about a number of these domains, they are significant in that they show that the nucleoplasm is not uniform mixture, but rather contains organized functional subdomains. Other subnuclear structures appear as part of abnormal disease processes. For example, the presence of small intranuclear rods has been reported in some cases of nemaline myopathy. This condition typically results from mutations in actin, and the rods themselves consist of mutant actin as well as other cytoskeletal proteins. Cajal bodies and gems A nucleus typically contains between 1 and 10 compact structures called Cajal bodies or coiled bodies (CB), whose diameter measures between 0.2m and 2.0m depending on the cell type and species. When seen under an electron microscope, they resemble balls of tangled thread and are dense foci of distribution for the protein coilin. CBs are involved in a number of different roles relating to RNA processing, specifically small nucleolar RNA (snoRNA) and small nuclear RNA (snRNA) maturation, and histone mRNA modification. Similar to Cajal bodies are Gemini of coiled bodies, or gems, whose name is derived from the Gemini constellation in reference to their close "twin" relationship with CBs. Gems are similar in size and shape to CBs, and in fact are virtually indistinguishable under the microscope. Unlike CBs, gems do not contain small nuclear ribonucleoproteins (snRNPs), but do contain a protein called survivor of motor neurons (SMN) whose function relates to snRNP

Cell nucleus biogenesis. Gems are believed to assist CBs in snRNP biogenesis, though it has also been suggested from microscopy evidence that CBs and gems are different manifestations of the same structure. RAFA and PTF domains RAFA domains, or polymorphic interphase karyosomal associations, were first described in microscopy studies in 1991. Their function was and remains unclear, though they were not thought to be associated with active DNA replication, transcription, or RNA processing.[3] They have been found to often associate with discrete domains defined by dense localization of the transcription factor PTF, which promotes transcription of snRNA. PML bodies Promyelocytic leukaemia bodies (PML bodies) are spherical bodies found scattered throughout the nucleoplasm, measuring around 0.11.0m. They are known by a number of other names, including nuclear domain 10 (ND10), Kremer bodies, and PML oncogenic domains. PML bodies are named after one of their major components, the Promyelocytic leukemia protein. They are often seen in the nucleus in association with Cajal bodies and cleavage bodies. PML bodies belong to the nuclear matrix, an ill-defined super-structure of the nucleus proposed to anchor and regulate many nuclear functions, including DNA replication, transcription, or epigenetic silencing. The PML protein is the key organizer of these domains that recruits an ever-growing number of proteins, whose only common known feature to date is their ability to be sumoylated. Yet, pml-/- mice (which have their PML gene deleted) cannot assemble nuclear bodies, develop normally and live well, demonstrating that PML bodies are dispensable for most basic biological functions. Paraspeckles Discovered by Fox et al. in 2002, paraspeckles are irregularly shaped compartments in the nucleus' interchromatin space. First documented in HeLa cells, where there are generally 1030 per nucleus, paraspeckles are now known to also exist in all human primary cells, transformed cell lines, and tissue sections. Their name is derived from their distribution in the nucleus; the "para" is short for parallel and the "speckles" refers to the splicing speckles to which they are always in close proximity. Paraspeckles are dynamic structures that are altered in response to changes in cellular metabolic activity. They are transcription dependent and in the absence of RNA Pol II transcription, the paraspeckle disappears and all of its associated protein components (PSP1, p54nrb, PSP2, CFI(m)68, and PSF) form a crescent shaped perinucleolar cap in the nucleolus. This phenomenon is demonstrated during the cell cycle. In the cell cycle, paraspeckles are present during interphase and during all of mitosis except for telophase. During telophase, when the two daughter nuclei are formed, there is no RNA Pol II transcription so the protein components instead form a perinucleolar cap. Splicing speckles Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells. At the fluorescence-microscope level they appear as irregular, punctate structures, which vary in size and shape, and when examined by electron microscopy they are seen as clusters of interchromatin granules. Speckles are dynamic structures, and both their protein and RNA-protein components can cycle continuously between speckles and other nuclear locations, including active transcription sites. Studies on the composition, structure and behaviour of speckles have provided a model for understanding the functional compartmentalization of the nucleus and the organization of the gene-expression machinery. splicing snRNPs and other splicing proteins necessary for pre-mRNA processing. Because of a cell's changing requirements, the composition and location of these bodies changes according to mRNA transcription and regulation via phosphorylation of specific proteins. The splicing speckles are also known as nuclear speckles (nuclear specks), splicing factor compartments (SF compartments), interchromatin granule clusters (IGCs), B snurposomes. B snurposomes are found in the amphibian oocyte nuclei and in Drosophila melanogaster embryos. B snurposomes


Cell nucleus appear alone or attached to the Cajal bodies in the electron micrographs of the amphibian nuclei. IGCs function as storage sites for the splicing factors. Perichromatin fibrils Perichromatin fibrils are visible only under electron microscope. They are located next to the transcriptionally active chromatin and is hypothesized to be the site of active pre-mRNA processing.


The nucleus provides a site for genetic transcription that is segregated from the location of translation in the cytoplasm, allowing levels of gene regulation that are not available to prokaryotes. The main function of the cell nucleus is to control gene expression and mediate the replication of DNA during the cell cycle.

Cell compartmentalization
The nuclear envelope allows the nucleus to control its contents, and separate them from the rest of the cytoplasm where necessary. This is important for controlling processes on either side of the nuclear membrane. In most cases where a cytoplasmic process needs to be restricted, a key participant is removed to the nucleus, where it interacts with transcription factors to downregulate the production of certain enzymes in the pathway. This regulatory mechanism occurs in the case of glycolysis, a cellular pathway for breaking down glucose to produce energy. Hexokinase is an enzyme responsible for the first the step of glycolysis, forming glucose-6-phosphate from glucose. At high concentrations of fructose-6-phosphate, a molecule made later from glucose-6-phosphate, a regulator protein removes hexokinase to the nucleus, where it forms a transcriptional repressor complex with nuclear proteins to reduce the expression of genes involved in glycolysis.[4] In order to control which genes are being transcribed, the cell separates some transcription factor proteins responsible for regulating gene expression from physical access to the DNA until they are activated by other signaling pathways. This prevents even low levels of inappropriate gene expression. For example, in the case of NF-B-controlled genes, which are involved in most inflammatory responses, transcription is induced in response to a signal pathway such as that initiated by the signaling molecule TNF-, binds to a cell membrane receptor, resulting in the recruitment of signalling proteins, and eventually activating the transcription factor NF-B. A nuclear localisation signal on the NF-B protein allows it to be transported through the nuclear pore and into the nucleus, where it stimulates the transcription of the target genes. The compartmentalization allows the cell to prevent translation of unspliced mRNA. Eukaryotic mRNA contains introns that must be removed before being translated to produce functional proteins. The splicing is done inside the nucleus before the mRNA can be accessed by ribosomes for translation. Without the nucleus, ribosomes would translate newly transcribed (unprocessed) mRNA, resulting in misformed and nonfunctional proteins.

Cell nucleus


Gene expression
Gene expression first involves transcription, in which DNA is used as a template to produce RNA. In the case of genes encoding proteins, that RNA produced from this process is messenger RNA (mRNA), which then needs to be translated by ribosomes to form a protein. As ribosomes are located outside the nucleus, mRNA produced needs to be exported. Since the nucleus is the site of transcription, it also contains a variety of proteins that either directly mediate transcription or are involved in regulating the process. These proteins include helicases, which unwind the double-stranded DNA molecule to facilitate access to it, RNA polymerases, which synthesize the growing RNA molecule, topoisomerases, which change the amount of supercoiling in DNA, helping it wind and unwind, as well as a large variety of transcription factors that regulate expression.
A micrograph of ongoing gene transcription of ribosomal RNA illustrating the growing primary transcripts. "Begin" indicates the 5' end of the DNA, where new RNA synthesis begins; "end" indicates the 3' end, where the primary transcripts are almost complete.

Processing of pre-mRNA

Newly synthesized mRNA molecules are known as primary transcripts or pre-mRNA. They must undergo post-transcriptional modification in the nucleus before being exported to the cytoplasm; mRNA that appears in the cytoplasm without these modifications is degraded rather than used for protein translation. The three main modifications are 5' capping, 3' polyadenylation, and RNA splicing. While in the nucleus, pre-mRNA is associated with a variety of proteins in complexes known as heterogeneous ribonucleoprotein particles (hnRNPs). Addition of the 5' cap occurs co-transcriptionally and is the first step in post-transcriptional modification. The 3' poly-adenine tail is only added after transcription is complete. RNA splicing, carried out by a complex called the spliceosome, is the process by which introns, or regions of DNA that do not code for protein, are removed from the pre-mRNA and the remaining exons connected to re-form a single continuous molecule. This process normally occurs after 5' capping and 3' polyadenylation but can begin before synthesis is complete in transcripts with many exons. Many pre-mRNAs, including those encoding antibodies, can be spliced in multiple ways to produce different mature mRNAs that encode different protein sequences. This process is known as alternative splicing, and allows production of a large variety of proteins from a limited amount of DNA.

Cell nucleus


Dynamics and regulation

Nuclear transport
The entry and exit of large molecules from the nucleus is tightly controlled by the nuclear pore complexes. Although small molecules can enter the nucleus without regulation, macromolecules such as RNA and proteins require association karyopherins called importins to enter the nucleus and exportins to exit. "Cargo" proteins that must be translocated from the cytoplasm to the nucleus contain short amino acid sequences known as nuclear localization signals, which are bound Macromolecules, such as RNA and proteins, are actively transported across the nuclear by importins, while those transported membrane in a process called the Ran-GTP nuclear transport cycle. from the nucleus to the cytoplasm carry nuclear export signals bound by exportins. The ability of importins and exportins to transport their cargo is regulated by GTPases, enzymes that hydrolyze the molecule guanosine triphosphate to release energy. The key GTPase in nuclear transport is Ran, which can bind either GTP or GDP (guanosine diphosphate), depending on whether it is located in the nucleus or the cytoplasm. Whereas importins depend on RanGTP to dissociate from their cargo, exportins require RanGTP in order to bind to their cargo. Nuclear import depends on the importin binding its cargo in the cytoplasm and carrying it through the nuclear pore into the nucleus. Inside the nucleus, RanGTP acts to separate the cargo from the importin, allowing the importin to exit the nucleus and be reused. Nuclear export is similar, as the exportin binds the cargo inside the nucleus in a process facilitated by RanGTP, exits through the nuclear pore, and separates from its cargo in the cytoplasm. Specialized export proteins exist for translocation of mature mRNA and tRNA to the cytoplasm after post-transcriptional modification is complete. This quality-control mechanism is important due to these molecules' central role in protein translation; mis-expression of a protein due to incomplete excision of exons or mis-incorporation of amino acids could have negative consequences for the cell; thus, incompletely modified RNA that reaches the cytoplasm is degraded rather than used in translation.

Cell nucleus


Assembly and disassembly

During its lifetime, a nucleus may be broken down, either in the process of cell division or as a consequence of apoptosis (the process of programmed cell death). During these events, the structural components of the nucleus the envelope and lamina can be systematically degraded. In most cells, the disassembly of the nuclear envelope marks the end of the prophase of mitosis. However, this disassembly of the nucleus is not a universal feature of mitosis and does not occur in all cells. Some unicellular eukaryotes (e.g., yeasts) undergo so-called closed mitosis, in which the nuclear envelope remains intact. In closed mitosis, the daughter chromosomes migrate to opposite poles of the nucleus, which then divides in two. The cells of higher eukaryotes, however, usually undergo open mitosis, which is characterized by breakdown of the nuclear envelope. The daughter chromosomes then migrate to opposite poles of the mitotic spindle, and new nuclei reassemble around them.

An image of a newt lung cell stained with fluorescent dyes during metaphase. The mitotic spindle can be seen, stained green, attached to the two sets of chromosomes, stained light blue. All chromosomes but one are already at the metaphase plate.

At a certain point during the cell cycle in open mitosis, the cell divides to form two cells. In order for this process to be possible, each of the new daughter cells must have a full set of genes, a process requiring replication of the chromosomes as well as segregation of the separate sets. This occurs by the replicated chromosomes, the sister chromatids, attaching to microtubules, which in turn are attached to different centrosomes. The sister chromatids can then be pulled to separate locations in the cell. In many cells, the centrosome is located in the cytoplasm, outside the nucleus; the microtubules would be unable to attach to the chromatids in the presence of the nuclear envelope. Therefore the early stages in the cell cycle, beginning in prophase and until around prometaphase, the nuclear membrane is dismantled. Likewise, during the same period, the nuclear lamina is also disassembled, a process regulated by phosphorylation of the lamins by protein kinases such as the CDC2 protein kinase. Towards the end of the cell cycle, the nuclear membrane is reformed, and around the same time, the nuclear lamina are reassembled by dephosphorylating the lamins. However, in dinoflagellates, the nuclear envelope remains intact, the centrosomes are located in the cytoplasm, and the microtubules come in contact with chromosomes, whose centromeric regions are incorporated into the nuclear envelope (the so-called closed mitosis with extranuclear spindle). In many other protists (e.g., ciliates, sporozoans) and fungi, the centrosomes are intranuclear, and their nuclear envelope also does not disassemle during cell division. Apoptosis is a controlled process in which the cell's structural components are destroyed, resulting in death of the cell. Changes associated with apoptosis directly affect the nucleus and its contents, for example, in the condensation of chromatin and the disintegration of the nuclear envelope and lamina. The destruction of the lamin networks is controlled by specialized apoptotic proteases called caspases, which cleave the lamin proteins and, thus, degrade the nucleus' structural integrity. Lamin cleavage is sometimes used as a laboratory indicator of caspase activity in assays for early apoptotic activity. Cells that express mutant caspase-resistant lamins are deficient in nuclear changes related to apoptosis, suggesting that lamins play a role in initiating the events that lead to apoptotic degradation of the nucleus. Inhibition of lamin assembly itself is an inducer of apoptosis. The nuclear envelope acts as a barrier that prevents both DNA and RNA viruses from entering the nucleus. Some viruses require access to proteins inside the nucleus in order to replicate and/or assemble. DNA viruses, such as herpesvirus replicate and assemble in the cell nucleus, and exit by budding through the inner nuclear membrane. This

Cell nucleus process is accompanied by disassembly of the lamina on the nuclear face of the inner membrane.


Disease-related dynamics
Initially, it has been suspected that immunoglobulins in general and autoantibodies in particular do not enter the nucleus. Now there is a body of evidence that under pathological conditions (e.g. lupus erythematosus) IgG can enter the nucleus.[5]

Anucleated and multinucleated cells

Although most cells have a single nucleus, some eukaryotic cell types have no nucleus, and others have many nuclei. This can be a normal process, as in the maturation of mammalian red blood cells, or a result of faulty cell division. Anucleated cells contain no nucleus and are, therefore, incapable of dividing to produce daughter cells. The best-known anucleated cell is the mammalian red blood cell, or erythrocyte, which also lacks other organelles such as mitochondria, and serves primarily as a transport vessel to ferry oxygen from the lungs to the body's tissues. Erythrocytes mature through erythropoiesis in the bone marrow, where they lose their nuclei, organelles, and ribosomes. The nucleus is expelled during the process of differentiation from an erythroblast to a reticulocyte, which is the immediate precursor of the mature erythrocyte. The presence of mutagens may induce the release of some immature "micronucleated" erythrocytes into the bloodstream. Anucleated cells can also arise from flawed cell division in which one daughter lacks a nucleus and the other has two nuclei.

Human red blood cells, like those of other mammals, lack nuclei. This occurs as a normal part of the cells' development.

Multinucleated cells contain multiple nuclei. Most acantharean species of protozoa and some fungi in mycorrhizae have naturally multinucleated cells. Other examples include the intestinal parasites in the genus Giardia, which have two nuclei per cell. In humans, skeletal muscle cells, called myocytes and syncytium, become multinucleated during development; the resulting arrangement of nuclei near the periphery of the cells allows maximal intracellular space for myofibrils. Multinucleated and binucleated cells can also be abnormal in humans; for example, cells arising from the fusion of monocytes and macrophages, known as giant multinucleated cells, sometimes accompany inflammation and are also implicated in tumor formation. A number of dinoflagelates are known to have two nuclei.[6] Unlike other multinucleated cells these nuclei contain two distinct lineages of DNA: one from the dinoflagelate and the other from a symbiotic diatom. Curiously the mitochondrion and the plastid of the diatom remain functional.

As the major defining characteristic of the eukaryotic cell, the nucleus' evolutionary origin has been the subject of much speculation. Four major hypotheses have been proposed to explain the existence of the nucleus, although none have yet earned widespread support. The first model known as the "syntrophic model" proposes that a symbiotic relationship between the archaea and bacteria created the nucleus-containing eukaryotic cell. (Organisms of the Archaea and Bacteria domain have no cell nucleus.[7]) It is hypothesized that the symbiosis originated when ancient archaea, similar to modern methanogenic archaea, invaded and lived within bacteria similar to modern myxobacteria, eventually forming the early nucleus. This theory is analogous to the accepted theory for the origin of eukaryotic mitochondria and chloroplasts, which are thought to have developed from a similar endosymbiotic relationship between proto-eukaryotes and aerobic bacteria.

Cell nucleus The archaeal origin of the nucleus is supported by observations that archaea and eukarya have similar genes for certain proteins, including histones. Observations that myxobacteria are motile, can form multicellular complexes, and possess kinases and G proteins similar to eukarya, support a bacterial origin for the eukaryotic cell. A second model proposes that proto-eukaryotic cells evolved from bacteria without an endosymbiotic stage. This model is based on the existence of modern planctomycetes bacteria that possess a nuclear structure with primitive pores and other compartmentalized membrane structures. A similar proposal states that a eukaryote-like cell, the chronocyte, evolved first and phagocytosed archaea and bacteria to generate the nucleus and the eukaryotic cell. The most controversial model, known as viral eukaryogenesis, posits that the membrane-bound nucleus, along with other eukaryotic features, originated from the infection of a prokaryote by a virus. The suggestion is based on similarities between eukaryotes and viruses such as linear DNA strands, mRNA capping, and tight binding to proteins (analogizing histones to viral envelopes). One version of the proposal suggests that the nucleus evolved in concert with phagocytosis to form an early cellular "predator". Another variant proposes that eukaryotes originated from early archaea infected by poxviruses, on the basis of observed similarity between the DNA polymerases in modern poxviruses and eukaryotes. It has been suggested that the unresolved question of the evolution of sex could be related to the viral eukaryogenesis hypothesis. A very recent proposal suggests that traditional variants of the endosymbiont theory are insufficiently powerful to explain the origin of the eukaryotic nucleus. This model, termed the exomembrane hypothesis, suggests that the nucleus instead originated from a single ancestral cell that evolved a second exterior cell membrane; the interior membrane enclosing the original cell then became the nuclear membrane and evolved increasingly elaborate pore structures for passage of internally synthesized cellular components such as ribosomal subunits.



Comparison of human and chimpanzee chromosomes.

Mouse chromosome territories in different cell types.

24 chromosome territories in human cells.

[1] Leeuwenhoek, A. van: Opera Omnia, seu Arcana Naturae ope exactissimorum Microscopiorum detecta, experimentis variis comprobata, Epistolis ad varios illustres viros. J. Arnold et Delphis, A. Beman, Lugdinum Batavorum 17191730. Cited after: Dieter Gerlach, Geschichte der Mikroskopie. Verlag Harry Deutsch, Frankfurt am Main, Germany, 2009. ISBN 978-3-8171-1781-9. [2] Online Version here (http:/ / www. t-cremer. de/ main_de/ cremer/ personen/ info_T_Cremer. htm#book) [3] PMID 1955462 [4] PMID 15667322 [5] Bhm I. IgG deposits can be detected in cell nuclei of patients with both lupus erythematosus and malignancy. Clin Rheumatol 2007;26(11) 1877-1882 [6] Imanian B, Pombert JF, Dorrell RG, Burki F, Keeling PJ (2012) Tertiary endosymbiosis in two dinotoms has generated little change in the mitochondrial genomes of their dinoflagellate hosts and diatom endosymbionts" PLoS One 7(8) e43763. [7] C.Michael Hogan. 2010. Archaea. eds. E.Monosson & C.Cleveland, Encyclopedia of Earth. National Council for Science and the Environment, Washington DC. (http:/ / www. eoearth. org/ article/ Archaea?topic=49496)

Cell nucleus


Further reading
Library resources
About Cell nucleus

Online books ( Resources in your library ( Resources in other libraries (

Goldman, Robert D.; Gruenbaum, Y; Moir, RD; Shumaker, DK; Spann, TP (2002). "Nuclear lamins: building blocks of nuclear architecture". Genes & Dev. 16 (5): 533547. doi: 10.1101/gad.960502 ( 1101/gad.960502). PMID 11877373 ( A review article about nuclear lamins, explaining their structure and various roles Grlich, Dirk; Kutay, U (1999). "Transport between the cell nucleus and the cytoplasm". Ann. Rev. Cell Dev. Biol. 15: 607660. doi: 10.1146/annurev.cellbio.15.1.607 ( 607). PMID 10611974 ( A review article about nuclear transport, explains the principles of the mechanism, and the various transport pathways Lamond, Angus I.; Earnshaw, WC (1998-04-24). "Structure and Function in the Nucleus". Science 280 (5363): 547553. doi: 10.1126/science.280.5363.547 ( PMID 9554838 ( A review article about the nucleus, explaining the structure of chromosomes within the organelle, and describing the nucleolus and other subnuclear bodies Pennisi E. (2004). "Evolutionary biology. The birth of the nucleus". Science 305 (5685): 766768. doi: 10.1126/science.305.5685.766 ( PMID 15297641 (http:// A review article about the evolution of the nucleus, explaining a number of different theories Pollard, Thomas D.; William C. Earnshaw (2004). Cell Biology. Philadelphia: Saunders. ISBN0-7216-3360-9. A university level textbook focusing on cell biology. Contains information on nucleus structure and function, including nuclear transport, and subnuclear domains

External links ( Website covering structure and function of the nucleus from the Department of Oncology at the University of Alberta. The Nuclear Protein Database] Information on nuclear components. The Nucleus Collection ( in the Image & Video Library ( of The American Society for Cell Biology (http://www. contains peer-reviewed still images and video clips that illustrate the nucleus. Nuclear Envelope and Nuclear Import Section (,62) from Landmark Papers in Cell Biology (, Joseph G. Gall, J. Richard McIntosh, eds., contains digitized commentaries and links to seminal research papers on the nucleus. Published online in the Image & Video Library ( of The American Society for Cell Biology ( Cytoplasmic patterns generated by human antibodies (




The nucleolus is contained within the cell nucleus.

Cell biology The animal cell

Components of a typical animal cell: 1. Nucleolus 2. Nucleus 3. Ribosome (little dots) 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus (or "Golgi body") 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytosol (fluid that contains organelles) 12. Lysosome 13. Centrosome 14. Cell membrane

The nucleolus is a structure found in the nucleus of cells. It is made up of proteins and nucleic acids found in the nucleus of eukaryotic cells. Its function is to transcribe ribosomal RNA (rRNA) and combine it with proteins to form

Nucleolus incomplete ribosomes. The nucleolus occupies up to about 25% of the volume of the cell nucleus. Malfunction of nucleoli can be the cause of several human diseases.[citation needed]


Three major components of the nucleolus are recognized: the fibrillar centers (FC), the dense fibrillar components (DFC), and granular component (GC). The DFC or pars fibrosa consists of newly transcribed rRNA bound to ribosomal proteins, while the GC, called pars granulosa, contains RNA bound to ribosomal proteins that are beginning to assemble into ribosomes. However, it has been proposed that this particular organization is only observed in higher eukaryotes and that it evolved from a bipartite organization with the transition from anamniotes to amniotes. Reflecting the substantial increase in the DNA intergenic region, an original fibrillar component would have separated into the FC and the DFC.[1] Another structure identified within many nucleoli (particularly in plants) is a clear area in the center of the structure referred to as a nucleolar vacuole. Nucleoli of various plant species have been shown to have very high concentrations of iron in contrast to human and animal cell nucleoli. The nucleolus ultrastructure can be visualized through an electron microscope, while the organization and dynamics can be studied through fluorescent protein tagging and fluorescent recovery after photobleaching (FRAP). Antibodies against the PAF49 protein can also be used as a marker for the nucleolus in immunofluorescence experiments.[2]

Function and ribosome assembly

Nucleoli are formed around specific genetic loci called nucleolar organizing regions (NORs), first described by Barbara McClintock. Because of this non-random organization, the nucleolus is defined as a "genetically determined element."[3] A NOR is composed of tandem repeats of rRNA genes, which can be found in several different chromosomes. The human genome, for example, contains more than 200 clustered copies of the rRNA genes on five different chromosomes (13, 14, 15, 21, 22). In a typical eukaryote and sometimes a prokaryote, an rRNA gene consists of a promoter, internal and external transcribed spacers (ITS/ETS), rRNA coding sequences (18S, 5.8S, 28S) and an external non-transcribed spacer.
Photomicrograph of nucleus and nucleolus In ribosome biogenesis, two of the three eukaryotic RNA polymerases (pol I and III) are required, and these function in a coordinated manner. In an initial stage, the rRNA genes are transcribed as a single unit within the nucleolus by RNA pol I or III. In order for this transcription to occur, several pol I-associated factors and DNA-specific transacting factors are required. In yeast, the most important are: UAF (upstream activating factor), TBP (tata-box binding protein), and CF (core factor), which bind promoter elements and form the preinitiation complex (PIC), which is in turn recognized by RNA pol. In humans, a similar PIC is assembled with SLI, the promoter selectivity factor (composed of TBP and TBP-associated factors, or TAFs), IFs (transcription initiation factors) and UBF (upstream

Nucleolus binding factor). RNA polymerase I transcribes most rRNA transcripts (28S, 18S, and 5.8S) but the 5S rRNA subunit (component of the 60S ribosomal subunit) is transcribed by RNA polymerase III. Transcription of the ribosomal gene yields a long precursor molecule (45S pre-rRNA) which still contains the ITS and ETS. Further processing is needed to generate the 18S RNA, 5.8S and 28S RNA molecules. In eukaryotes, the RNA-modifying enzymes are brought to their respective recognition sites by interaction with guide RNAs, which bind these specific sequences. These guide RNAs belong to the class of small nucleolar RNAs (snoRNAs) which are complexed with proteins and exist as small-nucleolar-ribonucleoproteins (snoRNPs). Once the rRNA subunits are processed, they are ready to be assembled into larger ribosomal subunits. However, an additional rRNA molecule, the 5S rRNA, is also necessary. In yeast, the 5S rDNA sequence is localized in the external non-transcribed spacer and is transcribed in the nucleolus by RNA pol. In higher eukaryotes and plants, the situation is more complex, for the 5S DNA sequence lies outside the NOR and is transcribed by RNA pol III in the nucleoplasm, after which it finds its way into the nucleolus to participate in the ribosome assembly. This assembly not only involves the rRNA, but ribosomal proteins as well. The genes encoding these r-proteins are transcribed by pol II in the nucleoplasm by a "conventional" pathway of protein synthesis (transcription, pre-mRNA processing, nuclear export of mature mRNA and translation on cytoplasmic ribosomes). The mature r-proteins are then "imported" back into the nucleus and finally the nucleolus. Association and maturation of rRNA and r-proteins result in the formation of the 40S (small) and 60S (large) subunits of the complete ribosome. These are exported through the nuclear pore complexes to the cytoplasm, where they remain free or become associated with the endoplasmic reticulum, forming rough endoplasmic reticulum (RER). A continuous chain between the nucleoplasm and the inner parts of the nucleolus exists through a network of nucleolar channels. In this way, macromolecules with a molecular weight up to 2000 kDa are easily distributed throughout the nucleolus. [citation needed]


Sequestration of proteins
In addition to its role in ribosomal biogenesis, the nucleolus is known to capture and immobilize proteins, a process known as nucleolar sequestration. Proteins that are sequestered in the nucleolus are unable to diffuse and to interact with their binding partners. Targets of this post-translational regulatory mechanism include VHL, PML, MDM2, RelA, HAND1 and hTERT, among many others. It is now known that long noncoding RNAs originating from intergenic regions of the nucleolus are responsible for this phenomenon.

[1] as PDF (http:/ / www. lafontainelab. com/ Suppl_data/ Thiry_2005/ S3. pdf) [2] PAF49 antibody | GeneTex Inc (http:/ / www. genetex. com/ PAF49-antibody-GTX102175. html). Retrieved on 2013-03-03. [3] as PDF (http:/ / www. jic. ac. uk/ staff/ peter-shaw/ pdfs/ raska intrevcytol 06. pdf)

External links
Cooper, Geoffrey M. (2000). "The Nucleolus" ( The Cell: A Molecular Approach ( (2nd ed.). Sunderland MA: Sinauer Associates. ISBN0-87893-106-6. Nucleolus under electron microscope II at ( workshop/EM/EMNucleolus.html) Nuclear Protein Database search under compartment ( compartment?page=nucleolus.html) Cell Nucleolus ( at the US National Library of Medicine Medical Subject Headings (MeSH) BU Histology Learning System: 20104loa (



The ribosome (from ribonucleic acid and the Greek soma, meaning "body") is a large and complex molecular machine, found within all living cells, that serves as the primary site of biological protein synthesis (translation). Ribosomes link amino acids together in the order specified by messenger RNA (mRNA) molecules. Ribosomes consist of two major subunitsthe small ribosomal subunit reads the mRNA, while the large subunit joins amino acids to form a The ribosome assembles polymeric protein molecules whose sequence is controlled by polypeptide chain. Each subunit is the sequence of messenger RNA molecules. This is required by all living cells and composed of one or more ribosomal associated viruses. RNA (rRNA) molecules and a variety of proteins. The ribosomes and associated molecules are also known as the translational apparatus. The sequence of DNA encoding for a protein may be copied many times into messenger RNA (mRNA) chains of a similar sequence. Ribosomes can bind to an mRNA chain and use it as a template for determining the correct sequence of amino acids in a particular protein. Amino acids are selected, collected and carried to the ribosome by transfer RNA (tRNA molecules), which enter one part of the ribosome and bind to the messenger RNA chain. The attached amino acids are then linked together by another part of the ribosome. Once the protein is produced, it can then 'fold' to produce a specific functional three-dimensional structure. A ribosome is made from complexes of RNAs and proteins and is therefore a ribonucleoprotein. Each ribosome is divided into two subunits: the smaller subunit binds to the mRNA pattern, while the larger subunit binds to the tRNA and the amino acids. When a ribosome finishes reading an mRNA molecule, these two subunits split apart. Ribosomes are ribozymes, because the catalytic peptidyl transferase activity that links amino acids together is performed by the ribosomal RNA. Ribosomes from bacteria, archaea and eukaryotes (the three domains of life on Earth) differ in their size, sequence, structure, and the ratio of protein to RNA. The differences in structure allow some antibiotics to kill bacteria by inhibiting their ribosomes, while leaving human ribosomes unaffected. In bacteria and archaea, more than one ribosome may move along a single mRNA chain at one time, each "reading" its sequence and producing a corresponding protein molecule. The ribosomes in the mitochondria of eukaryotic cells functionally resemble many features of those in bacteria, reflecting the likely evolutionary origin of mitochondria.



Ribosomes were first observed in the mid-1950s by Romanian cell biologist George Emil Palade using an electron microscope as dense particles or granules for which, in 1974, he would win a Nobel Prize. The term "ribosome" was proposed by scientist Richard B. Roberts in 1958: During the course of the symposium a semantic difficulty became apparent. To some of the participants, "microsomes" mean the ribonucleoprotein particles of the microsome fraction contaminated by other protein and lipid material; to others, the microsomes consist of protein and lipid contaminated by particles. The phrase microsomal particles does not seem adequate, and ribonucleoprotein particles of the microsome fraction is much too awkward. During the meeting, the word "ribosome" was suggested, which has a very satisfactory name and a pleasant sound. The present confusion would be eliminated if ribosome were adopted to designate ribonucleoprotein particles in sizes ranging from 35 to 100S. Roberts, R. B., Microsomal Particles and Protein Synthesis[1] Albert Claude, Christian de Duve, and George Emil Palade were jointly awarded the Nobel Prize in Physiology or Medicine, in 1974, for the discovery of the ribosomes. The Nobel Prize in Chemistry 2009 was awarded to Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for determining the detailed structure and mechanism of the ribosome.[2]

Ribosomes consist of two subunits that fit together (Figure 2) and work as one to translate the mRNA into a polypeptide chain during protein synthesis (Figure 1). Because they are formed from two subunits of non-equal size, they are slightly longer in the axis than in diameter. Prokaryotic ribosomes are around 20 nm (200 ) in diameter and are composed of 65% ribosomal RNA and 35% ribosomal proteins. Figure 2 : Large (red) and small (blue) subunit fit Eukaryotic ribosomes are between 25 and 30 nm (250300 ) in together diameter and the ratio of rRNA to protein is close to 1. Bacterial subunits consist of one or two and eukaryotic of one or three very large RNA molecules (known as ribosomal RNA or rRNA) and multiple smaller protein molecules.Crystallographic work has shown that there are no ribosomal proteins close to the reaction site for polypeptide synthesis. This proves that the protein components of ribosomes do not directly participate in peptide bond formation catalysis, but rather suggests that these proteins act as a scaffold that may enhance the ability of rRNA to synthesize protein (See: Ribozyme).



The ribosomal subunits of prokaryotes and eukaryotes are quite similar.[3] The unit of measurement is the Svedberg unit, a measure of the rate of sedimentation incentrifugation rather than size, and this accounts for why fragment names do not add up (70S is made of 50S and 30S). Prokaryotes have 70S ribosomes, each consisting of a small (30S) and a large (50S) subunit. Their small subunit has a 16S RNA subunit (consisting of 1540 nucleotides) bound to 21 proteins. The large subunit is composed of a 5S RNA subunit (120 nucleotides), a 23S RNA subunit (2900 nucleotides) and 31 proteins. Affinity label for the tRNA binding sites on the E. coli ribosome allowed the identification of A and P site proteins most likely Atomic structure of the 30S Subunit from Thermus thermophilus. Proteins are shown in associated with the peptidyltransferase blue and the single RNA chain in orange. activity; labelled proteins are L27, L14, L15, L16, L2; at least L27 is located at the donor site, as shown by E. Collatz and A.P. Czernilofsky. Additional research has demonstrated that the S1 and S21 proteins, in association with the 3'-end of 16S ribosomal RNA, are involved in the initiation of translation. Eukaryotes have 80S ribosomes, each consisting of a small (40S) and large (60S) subunit. Their 40S subunit has an 18S RNA (1900 nucleotides) and 33 proteins. The large subunit is composed of a 5S RNA (120 nucleotides), 28S RNA (4700 nucleotides), a 5.8S RNA (160 nucleotides) subunits and 46 proteins. During 1977, Czernilofsky published research that used affinity labeling to identify tRNA-binding sites on rat liver ribosomes. Several proteins, including L32/33, L36, L21, L23, L28/29 and L13 were implicated as being at or near the peptidyl transferase center. The ribosomes found in chloroplasts and mitochondria of eukaryotes also consist of large and small subunits bound together with proteins into one 70S particle. These organelles are believed to be descendants of bacteria (see Endosymbiotic theory) and as such their ribosomes are similar to those of bacteria.[4] The various ribosomes share a core structure, which is quite similar despite the large differences in size. Much of the RNA is highly organized into various tertiary structural motifs, for example pseudoknots that exhibit coaxial stacking. The extra RNA in the larger ribosomes is in several long continuous insertions, such that they form loops out of the core structure without disrupting or changing it.[3] All of the catalytic activity of the ribosome is carried out by theRNA; the proteins reside on the surface and seem to stabilize the structure. The differences between the bacterial and eukaryotic ribosomes are exploited by pharmaceutical chemists to create antibiotics that can destroy a bacterial infection without harming the cells of the infected person. Due to the differences in their structures, the bacterial 70S ribosomes are vulnerable to these antibiotics while the eukaryotic 80S ribosomes are not. Even though mitochondria possess ribosomes similar to the bacterial ones, mitochondria are not affected by these antibiotics because they are surrounded by a double membrane that does not easily admit these antibiotics into the organelle.[5]



High-resolution structure
The general molecular structure of the ribosome has been known since the early 1970s. In the early 2000s the structure has been achieved at high resolutions, on the order of a few . The first papers giving the structure of the ribosome at atomic resolution were published almost simultaneously in late 2000. The 50S (large prokaryotic) subunit was determined from the archaeons Haloarcula marismortui and Deinococcus radiodurans, and the structure of the 30S subunit was determined from Thermus thermophilus. These structural studies were awarded the Nobel Prize in Chemistry in 2009. Early the next year (May 2001) these coordinates were used to reconstruct the entire T. thermophilus 70S particle at 5.5 resolution.

Two papers were published in November 2005 with structures of the Escherichia coli 70S ribosome. The structures of a vacant ribosome were determined at 3.5- resolution using x-ray crystallography. Then, two weeks later, a structure based on cryo-electron microscopy was published, which depicts the ribosome at 1115 resolution in the act of passing a newly synthesized protein strand into the protein-conducting channel. The first atomic structures of the ribosome complexed with tRNA and mRNA molecules were solved by using X-ray crystallography by two groups independently, at 2.8 and at 3.7 . These structures allow one to see the details of interactions of the Thermus thermophilus ribosome with mRNA and with tRNAs bound at classical ribosomal sites. Interactions of the ribosome with long mRNAs containing Shine-Dalgarno sequences were visualized soon after that at 4.5- to 5.5- resolution. In 2011, the first complete atomic structure of the eukaryotic 80S ribosome from the yeastSaccharomyces cerevisiae was obtained by crystallography. The model reveals the architecture of eukaryote-specific elements and their interaction with the universally conserved core. At the same time, the complete model of a eukaryotic 40S ribosomal structure in Tetrahymena thermophila was published and described the structure of the40S subunit as well as much about the 40S subunit's interaction with eIF1 during translation initiation. Similarly, the eukaryotic 60S subunit structure was also determined from Tetrahymena thermophila in complex witheIF6.

Atomic structure of the 50S Subunit from Haloarcula marismortui. Proteins are shown in blue and the two RNA chains in orange and yellow. The small patch of green in the center of the subunit is the active site.



Ribosomes are the workhorses of protein biosynthesis, the process of translating mRNA into protein. The mRNA comprises a series of codons that dictate to the ribosome the sequence of the amino acids needed to make the protein. Using the mRNA as a template, the ribosome traverses each codon (3 nucleotides) of the mRNA, pairing it with the appropriate amino acid provided by an aminoacyl-tRNA. aminoacyl-tRNA contains a complementary anticodon on one end and the appropriate amino acid on the other. The small ribosomal subunit, typically bound to an aminoacyl-tRNA containing the amino acid methionine, binds to an AUG codon on the mRNA and recruits the large ribosomal subunit. The ribosome contains three RNA binding sites, designated A, P and E. The A site binds an aminoacyl-tRNA; the P site binds a peptidyl-tRNA (a tRNA bound to the peptide being synthesized); and the E site binds a free tRNA before it exits the ribosome. Protein synthesis begins at a start codon AUG near the 5' end of the mRNA. mRNA binds to the P site of the ribosome first. The ribosome is able to identify the start codon by use of the Shine-Dalgarno sequence of the mRNA in prokaryotes and Kozak box in eukaryotes. Although catalysis of the peptide bond involves the C2 hydroxyl of RNA's P-site (see Function section below) adenosine in a protein shuttle mechanism, other steps in protein synthesis (such as translocation) are caused by changes in protein conformations.Since their catalytic core is made of RNA, ribosomes are classified as "ribozymes,"and it is thought that they might be remnants of the RNA world.

Figure 3 : Translation of mRNA (1) by a ribosome (2)(shown as small and large subunits) into a polypeptide chain (3). The ribosome begins at the start codon of mRNA (AUG) and ends at the stop codon (UAG).

In Figure 3, both ribosomal subunits (small and large) assemble at the start codon (towards the 5' end of the mRNA). The ribosome uses tRNA that matches the current codon (triplet) on the mRNA to append an amino acid to the polypeptide chain. This is done for each triplet on the mRNA, while the ribosome moves towards the 3' end of the mRNA. Usually in bacterial cells, several ribosomes are working parallel on a single mRNA, forming what is called apolyribosome or polysome.

Ribosome locations
Ribosomes are classified as being either "free" or "membrane-bound". Free and membrane-bound ribosomes differ only in their spatial distribution; they are identical in structure. Whether the ribosome exists in a free or membrane-bound state depends on the presence of an ER-targeting signal sequence on the protein being synthesized, so an individual ribosome might be membrane-bound when it is making one protein, but free in the cytosol when it makes another protein. Ribosomes are sometimes referred to as organelles, but the use of the term organelle is often restricted to describing sub-cellular components that include a phospholipid membrane, which ribosomes, being entirely particulate, do not. For this reason, ribosomes may sometimes be described as "non-membranous organelles".



Free ribosomes
Free ribosomes can move about anywhere in the cytosol, but are excluded from the cell nucleus and other organelles. Proteins that are formed from free ribosomes are released into the cytosol and used within the cell. Since the cytosol contains high concentrations of glutathione and is, therefore, a reducing environment, proteins containing disulfide bonds, which are formed from oxidized cysteine residues, cannot be produced within it.

Membrane-bound ribosomes
When a ribosome begins to synthesize proteins that are needed in some organelles, the ribosome making this protein can become "membrane-bound". In eukaryotic cells this happens in a region of the endoplasmic reticulum (ER) called the "rough ER". The newly produced polypeptide chains are inserted directly into the ER by the ribosome undertaking vectorial synthesis and are then transported to their destinations, through the secretory pathway. Bound ribosomes usually produce proteins that are used within the plasma membrane or are expelled from the cell via exocytosis.[6]

In bacterial cells, ribosomes are synthesized in the cytoplasm through the transcription of multiple ribosome gene operons. In eukaryotes, the process takes place both in the cell cytoplasm and in the nucleolus, which is a region within the cell nucleus. The assembly process involves the coordinated function of over 200 proteins in the synthesis and processing of the four rRNAs, as well as assembly of those rRNAs with the ribosomal proteins.

[1] [2] [3] [4] [5] [6] Roberts, R. B., editor. (1958) "Introduction" in Microsomal Particles and Protein Synthesis. New York: Pergamon Press, Inc. 2009 Nobel Prize in Chemistry (http:/ / nobelprize. org/ nobel_prizes/ chemistry/ laureates/ 2009/ ), Nobel Foundation. The Molecular Biology of the Cell, fourth edition. Bruce Alberts, et al. Garland Science (2002) pg. 342 ISBN 0-8153-3218-1 The Molecular Biology of the Cell, fourth edition. Bruce Alberts, et al. Garland Science (2002) pg. 808 ISBN 0-8153-3218-1 O'Brien, T.W., The General Occurrence of 55S Ribosomes in Mammalian Liver Mitochondria. J. Biol. Chem., 245:3409 (1971). http:/ / www. ncbi. nlm. nih. gov/ books/ NBK26841/ #A2204

External links
Lab computer simulates ribosome in motion ( motion/2100-11395_3-5907401.html) Role of the Ribosome (, Gwen V. Childs, copied here ( Ribosome ( in Proteopedia (http://www. - The free, collaborative 3D encyclopedia of proteins & other molecules Ribosomal proteins families in ExPASy ( Molecule of the Month ( index.html) RCSB Protein Data Bank ( Ribosome ( html) Elongation Factors ( pdb81_1.html) Palade ( 3D electron microscopy structures of ribosomes at the EM Data Bank(EMDB) ( emsearch/ribosome)

Ribosome This article incorporatespublic domain material from the NCBI document "Science Primer" (http:/ / www. ncbi.


Vesicle (biology and chemistry)

In cell biology, a vesicle is a small bubble within a cell, and thus a type of organelle. Enclosed by lipid bilayer, vesicles can form naturally, for example, during endocytosis. Alternatively, they may be prepared artificially, in which case they are called liposomes. If there is only one phospholipid bilayer, they are called unilamellar vesicles; otherwise they are called multilamellar. The membrane enclosing the vesicle is similar to that of the plasma membrane, and vesicles can fuse with the plasma membrane to release their contents outside of the cell. Vesicles can also fuse with other organelles within the cell.

Vesicles perform a variety of functions. Because it is separated from the cytosol, the inside of the vesicle can be made to be different from the cytosolic environment. For this reason, vesicles are a basic tool used by the cell for organizing cellular substances. Vesicles are involved in metabolism, transport, buoyancy control, and enzyme storage. They can also act as chemical reaction chambers.
IUPAC definition Closed structure formed by amphiphilic molecules that contains solvent (usually water).

Scheme of a liposome formed by phospholipids in an aqueous solution.

The 2013 Nobel Prize in Physiology or Medicine was shared by James Rothman, Randy Schekman, and Thomas Sdhof for their roles (building upon earlier research, some of it by their mentors) on the makeup and function of cell vesicles, especially in yeasts and in humans, including information on each vesicle's parts and how they are assembled. When cell vesicles, which help maintain a balance or equilibrium inside and outside of the blood vessels and cells (between the Sarfus image of lipid vesicles. intravascular and extravascular spaces and the intracellular and extracellular spaces, respectively), malfunction, potentially serious and often fatal conditions are the result. The dysfunction is thought to contribute to Alzheimer's disease, diabetes, some hard-to-treat cases of epilepsy, some cancers and immunological disorders, and certain neurovascular conditions. These are likely either caused, influenced, or made worse, by the disorders of the cell vesicles.[1]

Vesicle (biology and chemistry)


Types of vesicles
Vacuoles are vesicles which contain mostly water. Plant cells have a large central vacuole in the center of the cell that is used for osmotic control and nutrient storage. Contractile vacuoles are found in certain protists, especially those in Phylum Ciliophora. These vacuoles take water from the cytoplasm and excrete it from the cell to avoid bursting due to osmotic pressure.

Lysosomes are involved in cellular digestion. Food can be taken from outside the cell into food vacuoles by a process called endocytosis. These food vacuoles fuse with lysosomes which break down the components so that they can be used in the cell. This form of cellular eating is called phagocytosis.

Electron micrograph of a cell containing a food vacuole (fv) and transport vacuole (TV) in a malaria parasite.

Lysosomes are also used to destroy defective or damaged organelles in a process called autophagy. They fuse with the membrane of the damaged organelle, digesting it.

Transport vesicles
Transport vesicles can move molecules between locations inside the cell, e.g., proteins from the rough endoplasmic reticulum to the Golgi apparatus. Membrane-bound and secreted proteins are made on ribosomes found in the rough endoplasmic reticulum. Most of these proteins mature in the Golgi apparatus before going to their final destination which may be to lysosomes, peroxisomes, or outside of the cell. These proteins travel within the cell inside of transport vesicles.

Secretory vesicles
Secretory vesicles contain materials that are to be excreted from the cell. Cells have many reasons to excrete materials. One reason is to dispose of wastes. Another reason is tied to the function of the cell. Within a larger organism, some cells are specialized to produce certain chemicals. These chemicals are stored in secretory vesicles and released when needed. Types of secretory vesicles Synaptic vesicles are located at presynaptic terminals in neurons and store neurotransmitters. When a signal comes down an axon, the synaptic vesicles fuse with the cell membrane releasing the neurotransmitter so that it can be detected by receptor molecules on the next nerve cell. In animals endocrine tissues release hormones into the bloodstream. These hormones are stored within secretory vesicles. A good example is the endocrine tissue found in the islets of Langerhans in the pancreas. This tissue contains many cell types that are defined by which hormones they produce.

Vesicle (biology and chemistry) Secretory vesicles hold the enzymes that are used to make the cell walls of plants, protists, fungi, bacteria, and Archaea cells as well as the extracellular matrix of animal cells.


Other types of vesicles

Gas vesicles are used by Archaea, bacteria and planktonic microorganisms, possibly to control vertical migration by regulating the gas content and thereby buoyancy, or possibly to position the cell for maximum solar light harvesting. Matrix vesicles are located within the extracellular space, or matrix. Using electron microscopy they were discovered independently in 1967 by H. Clarke Anderson and Ermanno Bonucci. These cell-derived vesicles are specialized to initiate biomineralisation of the matrix in a variety of tissues, including bone, cartilage, and dentin. During normal calcification, a major influx of calcium and phosphate ions into the cells accompanies cellular apoptosis (genetically determined self-destruction) and matrix vesicle formation. Calcium-loading also leads to formation of phosphatidylserine:calcium:phosphate complexes in the plasma membrane mediated in part by a protein called annexins. Matrix vesicles bud from the plasma membrane at sites of interaction with the extracellular matrix. Thus, matrix vesicles convey to the extracellular matrix calcium, phosphate, lipids and the annexins which act to nucleate mineral formation. These processes are precisely coordinated to bring about, at the proper place and time, mineralization of the tissue's matrix unless the Golgi are non-existent. Multivesicular body, or MVB, is a membrane-bound vesicle containing a number of smaller vesicles.

Vesicle formation and transport

Cell biology The animal cell

Components of a typical animal cell: 1. Nucleolus 2. Nucleus 3. Ribosome (little dots) 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus (or "Golgi body") 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytosol (fluid that contains organelles) 12. Lysosome 13. Centrosome 14. Cell membrane

Vesicle (biology and chemistry) Some vesicles are made when part of the membrane pinches off the endoplasmic reticulum or the Golgi complex. Others are made when an object outside of the cell is surrounded by the cell membrane.


Capturing cargo molecules

The assembly of vesicles requires numerous coats to surround and bind to the proteins being transported; these bind to the coat vesicle. They also trap various transmembrane receptor proteins, called cargo receptors, which in turn trap the cargo molecules.

Vesicle coat
The vesicle coat serves to sculpt the curvature of a donor membrane, and to select specific proteins as cargo. It selects cargo proteins by binding to sorting signals. In this way the vesicle coat clusters selected membrane cargo proteins into nascent vesicle buds. There are three types of vesicle coats: clathrin, COPI, and COPII. Clathrin coats are found on vesicles trafficking between the Golgi and plasma membrane, the Golgi and endosomes, and the plasma membrane and endosomes. COPI coated vesicles are responsible for retrograde transport from the Golgi to the ER, while COPII coated vesicles are responsible for anterograde transport from the ER to the Golgi. The clathrin coat is thought to assemble in response to regulatory G protein. A coatomer coat assembles and disassembles due to an ADP ribosylation factor (ARF) protein.

Vesicle docking
Surface markers called SNAREs identify the vesicle's cargo, and complementary SNAREs on the target membrane act to cause fusion of the vesicle and target membrane. Such v-SNARES are hypothesised to exist on the vesicle membrane, while the complementary ones on the target membrane are known as t-SNAREs. Often SNAREs associated with vesicles or target membranes are instead classified as Qa, Qb, Qc, or R SNAREs owing to further variation than simply v- or t-SNAREs. An array of different SNARE complexes can be seen in different tissues and subcellular compartments, with 36 isoforms currently identified in humans. Regulatory Rab proteins are thought to inspect the joining of the SNAREs. Rab protein is a regulatory GTP-binding protein, and controls the binding of these complementary SNAREs for a long enough time for the Rab protein to hydrolyse its bound GTP and lock the vesicle onto the membrane.

Vesicle fusion
Vesicle fusion can occur in one of two ways: full fusion or kiss-and-run fusion. Fusion requires the two membranes to be brought within 1.5nm of each other. For this to occur water must be displaced from the surface of the vesicle membrane. This is energetically unfavorable, and evidence suggests that the process requires ATP, GTP, and acetyl-coA, fusion is also linked to budding, which is why the term budding and fusing arises.

Vesicles in receptor downregulation

Membrane proteins serving as receptors are sometimes tagged for downregulation by the attachment of ubiquitin. After arriving an endosome via the pathway described above, vesicles begin to form inside the endosome, taking with them the membrane proteins meant for degradation; When the endosome either matures to become a lysosome or is united with one, the vesicles are completely degraded. Without this mechanism, only the extracellular part of the membrane proteins would reach the lumen of the lysosome, and only this part would be degraded. It is because of these vesicles that the endosome is sometimes known as a multivesicular body. The pathway to their formation is not completely understood; unlike the other vesicles described above, the outer surface of the vesicles is not in contact with the cytosol.

Vesicle (biology and chemistry)


Vesicle preparation
Isolated vesicles Producing membrane vesicles is one of the methods to investigate various membranes of the cell. After the living tissue is crushed into suspension, various membranes form tiny closed bubbles. Big fragments of the crushed cells can be later discarded by low speed centrifugation and later the fraction of the known origin (plasmalemma, tonoplast, etc.) can be isolated by precise high-speed centrifugation in the density gradient. Using osmotic shock, it is possible temporarily open vesicles (filling in them with the required solution) and then centrifugate down again and resuspend in a different solution. Applying ionophores like valinomycin can create electrochemic gradients that are comparable to the gradients inside the living cell. Vesicles are mainly used in two types of research: To find and later isolate membrane receptors that specifically bind hormones and various other important substances. To investigate transport of various ions or other substances across the membrane of the given type. While the transport can be easier investigated with patch clamp techniques, vesicles can also be isolated from objects for that the patch clamp is not applicable.

Artificial vesicles
Phospholipid vesicles have also been studied in biochemistry. For such studies, a homogeneous phospholipid vesicle suspension can be prepared by sonication, injection of a phospholipid solution into the aqueous buffer solution membranes. In this way aqueous vesicle solutions can be prepared of different phospholipid composition, as well as different sizes of vesicles.

[1] 2013 Nobel Prize in Physiology or Medicine (http:/ / www. nobelprize. org/ nobel_prizes/ medicine/ laureates/ 2013/ press. html), press release 2013-10-07

Further reading
Alberts, Bruce; et al. (1998). Molecular Biology of the Cell (Fourth ed.). New York: Garland. ISBN0-8153-2971-7.

External links
Lipids, Membranes and Vesicle Trafficking - The Virtual Library of Biochemistry and Cell Biology (http://

Endoplasmic reticulum


Endoplasmic reticulum
The endoplasmic reticulum (ER) is a type of organelle in the cells of eukaryotic organisms that forms an interconnected network of flattened, membrane-enclosed sacs or tubes known as cisternae. The membranes of the ER are continuous with the outer membrane of the nuclear envelope. Endoplasmic reticulum occurs in most types of eukaryotic cell but is absent from red blood cells and spermatozoa. There are two types of endoplasmic reticulum, rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER). The outer (cytosolic) face of the rough endoplasmic Micrograph of rough endoplasmic reticulum network around the nucleus (shown in reticulum is studded with ribosomes that are lower right-hand side of the picture). Dark small circles in the network are the sites of protein synthesis. Rough mitochondria. endoplasmic reticulum is especially prominent in cells such as hepatocytes where active protein synthesis occurs. The smooth endoplasmic reticulum lacks ribosomes and functions in lipid metabolism, carbohydrate metabolism, and detoxification[citation needed] and is especially abundant in mammalian liver and gonad cells. The lacey membranes of the endoplasmic reticulum were first seen in 1945 by Keith R. Porter, Albert Claude, and Ernest F. Fullam.

Endoplasmic reticulum


The general structure of the endoplasmic reticulum is a membranous network of cisternae (sac-like structures) held together by the cytoskeleton. The phospholipid membrane encloses a space, the cisternal space (or lumen), which is continuous with the perinuclear space but separate from the cytosol. The functions of the endoplasmic reticulum can be summarized as the synthesis and export of proteins and membrane lipids, but varies between ER and cell type and cell function. The quantity of RER and SER in a cell can slowly interchange from one type to the other, depending on the changing metabolic activities of the cell. Transformation can include embedding of new proteins in membrane as well as structural changes. Changes in protein content may occur without noticeable structural changes.[citation
needed] 1Nucleus 2Nuclear pore 3Rough endoplasmic reticulum (RER) 4Smooth endoplasmic reticulum (SER) 5Ribosome on the rough ER 6Proteins that are transported 7Transport vesicle 8Golgi apparatus 9Cis face of the Golgi apparatus 10Trans face of the Golgi apparatus 11Cisternae of the Golgi apparatus

Rough endoplasmic reticulum

The surface of the rough endoplasmic reticulum (often abbreviated RER) is studded with protein-manufacturing ribosomes giving it a "rough" appearance (hence its name). The binding site of the ribosome on the rough endoplasmic reticulum is the translocon. However, the ribosomes bound to it at any one time are not a stable part of this organelle's structure as they are constantly being bound and released from the membrane. A ribosome only binds to the RER once a specific 3D rendering of endoplasmic reticulum protein-nucleic acid complex forms in the cytosol. This special complex forms when a free ribosome begins translating the mRNA of a protein destined for the secretory pathway. The first 5-30 amino acids polymerized encode a signal peptide, a molecular message that is recognized and bound by a signal recognition particle (SRP). Translation pauses and the ribosome complex binds to the RER translocon where translation continues with the nascent protein forming into the RER lumen and/or membrane. The protein is processed in the ER lumen by an enzyme (a signal peptidase), which removes the signal peptide. Ribosomes at this point may be released back into the cytosol; however, non-translating ribosomes are also known to stay associated with translocons.

Endoplasmic reticulum The membrane of the rough endoplasmic reticulum forms large double membrane sheets that are located near, and continuous with, the outer layer of the nuclear envelope. Although there is no continuous membrane between the endoplasmic reticulum and the Golgi apparatus, membrane-bound vesicles shuttle proteins between these two compartments.[1] Vesicles are surrounded by coating proteins called COPI and COPII. COPII targets vesicles to the Golgi apparatus and COPI marks them to be brought back to the rough endoplasmic reticulum. The rough endoplasmic reticulum works in concert with the Golgi complex to target new proteins to their proper destinations. A second method of transport out of the endoplasmic reticulum involves areas called membrane contact sites, where the membranes of the endoplasmic reticulum and other organelles are held closely together, allowing the transfer of lipids and other small molecules. The rough endoplasmic reticulum is key in multiple functions: Manufacture of lysosomal enzymes with a mannose-6-phosphate marker added in the cis-Golgi network[citation


Manufacture of secreted proteins, either secreted constitutively with no tag or secreted in a regulatory manner involving clathrin and paired basic amino acids in the signal peptide. Integral membrane proteins that stay embedded in the membrane as vesicles exit and bind to new membranes. Rab proteins are key in targeting the membrane; SNAP and SNARE proteins are key in the fusion event. Initial glycosylation as assembly continues. This is N-linked (O-linking occurs in the Golgi). N-linked glycosylation: If the protein is properly folded, glycosyltransferase recognizes the AA sequence NXS or NXT (with the S/T residue phosphorylated) and adds a 14-sugar backbone (2-N-acetylglucosamine, 9-branching mannose, and 3-glucose at the end) to the side-chain nitrogen of Asn.

Smooth endoplasmic reticulum

The smooth endoplasmic reticulum (abbreviated SER) has functions in several metabolic processes. It synthesizes lipids, phospholipids, and steroids. Cells which secrete these products, such as those in the testes, ovaries, and skin oil glands have a great deal of smooth endoplasmic reticulum. It also carries out the metabolism of carbohydrates, drug detoxification, attachment of receptors on cell membrane proteins, and steroid metabolism. In muscle cells, it regulates calcium ion concentration. It is connected to the nuclear envelope. Smooth endoplasmic reticulum is found in a variety of cell types (both animal and plant), and it serves different functions in each. The smooth endoplasmic reticulum also contains the enzyme glucose-6-phosphatase, which converts glucose-6-phosphate to glucose, a step in gluconeogenesis. It consists of tubules that are located near the cell periphery. These tubes sometimes branch forming a network that is reticular in appearance. In some cells, there are dilated areas like the sacs of rough endoplasmic reticulum. The network of smooth endoplasmic reticulum allows for an increased surface area to be devoted to the action or storage of key enzymes and the products of these enzymes.[citation needed] Sarcoplasmic reticulum The sarcoplasmic reticulum (SR), from the Greek sarx, ("flesh"), is smooth ER found in smooth and striated muscle. The only structural difference between this organelle and the smooth endoplasmic reticulum is the medley of proteins they have, both bound to their membranes and drifting within the confines of their lumens. This fundamental difference is indicative of their functions: The endoplasmic reticulum synthesizes molecules, while the sarcoplasmic reticulum stores and pumps calcium ions. The sarcoplasmic reticulum contains large stores of calcium, which it sequesters and then releases when the muscle cell is stimulated. It plays a major role in excitation-contraction coupling.[citation needed]

Endoplasmic reticulum


The endoplasmic reticulum serves many general functions, including the folding of protein molecules in sacs called cisternae and the transport of synthesized proteins in vesicles to the Golgi apparatus. Correct folding of newly made proteins is made possible by several endoplasmic reticulum chaperone proteins, including protein disulfide isomerase (PDI), ERp29, the Hsp70 family member BiP/Grp78, calnexin, calreticulin, and the peptidylpropyl isomerase family. Only properly folded proteins are transported from the rough ER to the Golgi apparatus. Disturbances in redox regulation, calcium regulation, glucose deprivation, and viral infection or the over-expression of proteins can lead to endoplasmic reticulum stress (ER stress), a state in which the folding of proteins slows, leading to an increase in unfolded proteins. This stress is emerging as a potential cause of damage in hypoxia/ischemia, insulin resistance, and other disorders.[citation needed]

Protein transport
Secretory proteins, mostly glycoproteins, are moved across the endoplasmic reticulum membrane. Proteins that are transported by the endoplasmic reticulum throughout the cell are marked with an address tag called a signal sequence. The N-terminus (one end) of a polypeptide chain (i.e., a protein) contains a few amino acids that work as an address tag, which are removed when the polypeptide reaches its destination. Proteins that are destined for places outside the endoplasmic reticulum are packed into transport vesicles and moved along the cytoskeleton toward their destination. The endoplasmic reticulum is also part of a protein sorting pathway. It is, in essence, the transportation system of the eukaryotic cell. The majority of its resident proteins are retained within it through a retention motif. This motif is composed of four amino acids at the end of the protein sequence. The most common retention sequence is KDEL (lys-asp-glu-leu). However, variation on KDEL does occur and other sequences can also give rise to endoplasmic reticulum retention. It is not known whether such variation can lead to sub-ER localizations. There are three KDEL receptors in mammalian cells, and they have a very high degree of sequence identity. The functional differences between these receptors remain to be established. [citation needed]

[1] Endoplasmic reticulum. (n.d.). McGraw-Hill Encyclopedia of Science and Technology. Retrieved September 13, 2006, from Web site: http:/ / www. answers. com/ topic/ endoplasmic-reticulum

External links
Lipid and protein composition of Endoplasmic reticulum ( php?membrane=Endoplasmic reticulum membrane) in OPM database Animations of the various cell functions referenced here (

Golgi apparatus


Golgi apparatus
The Golgi apparatus (/oldi/), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. It was identified in 1897 by the Italian physician Camillo Golgi and named after him in 1898. Part of the cellular endomembrane system, the Golgi apparatus packages proteins inside the cell before they are sent to their destination; it is particularly important in the processing of proteins for secretion.


Owing to its large size, the Golgi apparatus was one of the first organelles to be discovered and observed in detail. It was discovered in 1898 by Italian physician Camillo Golgi during an investigation of the nervous system. After first observing it under his microscope, he termed the structure the internal reticular apparatus. Some doubted the discovery at first, arguing that the appearance of the structure was merely an optical illusion created by the observation technique used by Golgi. With the development of modern microscopes in the 20th century, the discovery was confirmed. Early references to the Golgi referred to it by various names including the "GolgiHolmgren apparatus", "GolgiHolmgren ducts", and "GolgiKopsch apparatus". The term "Golgi apparatus" was used in 1910 and first appeared in scientific literature in 1913.

Micrograph of Golgi apparatus, visible as a stack of semicircular black rings near the bottom. Numerous circular vesicles can be seen in proximity to the organelle.

Golgi apparatus


Found within the cytoplasm of both plant and animal cells, the Golgi is composed of stacks of membrane-bound structures known as cisternae (singular: cisterna). An individual stack is sometimes called a dictyosome (from Greek dictyon: net + soma: body), especially in plant cells. A mammalian cell typically contains 40 to 100 stacks. Between four and eight cisternae are usually present in a stack; however, in some protists as many as sixty have been observed. Each cisterna comprises a flat, membrane enclosed disc that includes special Golgi enzymes which modify or help to modify cargo proteins that travel through it.

Diagram of the Golgi apparatus

The cisternae stack has four functional regions: the cis-Golgi network, medial-Golgi, endo-Golgi, and trans-Golgi network. Vesicles from the endoplasmic reticulum (via the vesicular-tubular clusters) fuse with the network and subsequently progress through the stack to the trans Golgi network, where they are packaged and sent to their destination. Each region contains different enzymes which 3D Rendering of Golgi Apparatus selectively modify the contents depending on where they reside. The cisternae also carry structural proteins important for their maintenance as flattened membranes which stack upon each other.

Function of a golgi body

Cells synthesize a large number of different macromolecules. The Golgi apparatus is integral in modifying, sorting, and packaging these macromolecules for cell secretion (exocytosis) or use within the cell. It primarily modifies proteins delivered from the rough endoplasmic reticulum but is also involved in the transport of lipids around the cell, and the creation of lysosomes. In this respect it can be thought of as similar to a post office; it packages and labels items which it then sends to different parts of the cell. Enzymes within the cisternae are able to modify the proteins by addition of carbohydrates (glycosylation) and phosphates (phosphorylation). In order to do so, the Golgi imports substances such as nucleotide sugars from the cytosol. These modifications may also form a signal sequence which determines the final destination of the protein. For example, the Golgi apparatus adds a mannose-6-phosphate label to proteins destined for lysosomes.

Golgi apparatus The Golgi plays an important role in the synthesis of proteoglycans, which are molecules present in the extracellular matrix of animals. It is also a major site of carbohydrate synthesis. This includes the production of glycosaminoglycans (GAGs), long unbranched polysaccharides which the Golgi then attaches to a protein synthesised in the endoplasmic reticulum to form proteoglycans. Enzymes in the Golgi polymerize several of these GAGs via a xylose link onto the core protein. Another task of the Golgi involves the sulfation of certain molecules passing through its lumen via sulfotranferases that gain their sulfur molecule from a donor called PAPS. This process occurs on the GAGs of proteoglycans as well as on the core protein. Sulfation is generally performed in the trans-Golgi network. The level of sulfation is very important to the proteoglycans' signalling abilities as well as giving the proteoglycan its overall negative charge. The phosphorylation of molecules requires that ATP is imported into the lumen of the Golgi and utilised by resident kinases such as casein kinase 1 and casein kinase 2. One molecule that is phosphorylated in the Golgi is Apolipoprotein, which forms a molecule known as VLDL that is a constituent of blood serum. It is thought that the phosphorylation of these molecules is important to help aid in their sorting for secretion into the blood serum. The Golgi has a putative role in apoptosis, with several Bcl-2 family members localised there, as well as to the mitochondria. A newly characterized protein, GAAP (Golgi anti-apoptotic protein), almost exclusively resides in the Golgi and protects cells from apoptosis by an as-yet undefined mechanism.


Vesicular transport
The vesicles that leave the rough endoplasmic reticulum are transported to the cis face of the Golgi apparatus, where they fuse with the Golgi membrane and empty their contents into the lumen. Once inside the lumen, the molecules are modified, then sorted for transport to their next destinations. The Golgi apparatus tends to be larger and more numerous in cells that synthesize and secrete large amounts of substances; for example, the plasma B cells and the antibody-secreting cells of the immune system have prominent Golgi complexes. Those proteins destined for areas of the cell other than either the endoplasmic reticulum or Golgi apparatus are moved towards the trans face, to a complex network of membranes and associated vesicles known as the trans-Golgi network (TGN). This area of the Golgi is the point at which proteins are sorted and shipped to their intended destinations by their placement into one of at least three different types of vesicles, depending upon the molecular marker they carry.

Diagram of secretory process from endoplasmic reticulum (orange) to Golgi apparatus (pink). 1. Nuclear membrane; 2. Nuclear pore; 3. Rough endoplasmic reticulum (RER); 4. Smooth endoplasmic reticulum (SER); 5. Ribosome attached to RER; 6. Macromolecules; 7. Transport vesicles; 8. Golgi apparatus; 9. Cis face of Golgi apparatus; 10. Trans face of Golgi apparatus; 11. Cisternae of the Golgi Apparatus

Golgi apparatus


Types Exocytotic vesicles (continuous) Secretory vesicles (regulated)

Description Vesicle contains proteins destined for extracellular release. After packaging, the vesicles bud off and immediately move towards the plasma membrane, where they fuse and release the contents into the extracellular space in a process known as constitutive secretion. Vesicle contains proteins destined for extracellular release. After packaging, the vesicles bud off and are stored in the cell until a signal is given for their release. When the appropriate signal is received they move towards the membrane and fuse to release their contents. This process is known as regulated secretion. Vesicle contains proteins and ribosomes destined for the lysosome, an organelle of degradation containing many acid hydrolases, or to lysosome-like storage organelles. These proteins include both digestive enzymes and membrane proteins. The vesicle first fuses with the late endosome, and the contents are then transferred to the lysosome via unknown mechanisms.

Example Antibody release by activated plasma B cells

Neurotransmitter release from neurons

Lysosomal vesicles

Digestive proteases destined for the lysosome

Transport mechanism
The transport mechanism which proteins use to progress through the Golgi apparatus is not yet clear; however a number of hypotheses currently exist. Until recently, the vesicular transport mechanism was favoured but now more evidence is coming to light to support cisternal maturation. The two proposed models may actually work in conjunction with each other, rather than being mutually exclusive. This is sometimes referred to as the combined model. Cisternal maturation model: the cisternae of the Golgi apparatus move by being built at the cis face and destroyed at the trans face. Vesicles from the endoplasmic reticulum fuse with each other to form a cisterna at the cis face, consequently this cisterna would appear to move through the Golgi stack when a new cisterna is formed at the cis face. This model is supported by the fact that structures larger than the transport vesicles, such as collagen rods, were observed microscopically to progress through the Golgi apparatus. This was initially a popular hypothesis, but lost favour in the 1980s. Recently it has made a comeback, as laboratories at the University of Chicago and the University of Tokyo have been able to use new technology to directly observe Golgi compartments maturing. Additional evidence comes from the fact that COPI vesicles move in the retrograde direction, transporting endoplasmic reticulum proteins back to where they belong by recognizing a signal peptide. Vesicular transport model: Vesicular transport views the Golgi as a very stable organelle, divided into compartments in the cis to trans direction. Membrane bound carriers transport material between the endoplasmic reticulum and the different compartments of the Golgi. Experimental evidence includes the abundance of small vesicles (known technically as shuttle vesicles) in proximity to the Golgi apparatus. To direct the vesicles, actin filaments connect packaging proteins to the membrane to ensure that they fuse with the correct compartment.

Golgi apparatus


Fate during mitosis

In animal cells, the Golgi apparatus will break up and disappear following the onset of mitosis, or cellular division. During the telophase of mitosis, the Golgi apparatus reappears. As of December 2009[1] it is uncertain how this occurs. In contrast, Golgi stacks have been observed to remain intact in plant or yeast cells throughout the cell cycle. The reason for this difference is not yet known, but it may, in part, be a consequence of golgin proteins.

[1] http:/ / en. wikipedia. org/ w/ index. php?title=Golgi_apparatus& action=edit

The cytoskeleton (also CSK) is a cellular scaffolding or skeleton contained within a cell's cytoplasm. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton. It forms structures such as flagella, cilia and lamellipodia and plays important roles in both intracellular transport (the movement of vesicles and organelles, for example) and cellular division. In 1903 Nikolai K Koltsov proposed that the shape of cells was determined by a network of tubules which he termed the cytoskeleton. The concept of a protein mosaic that dynamically coordinated cytoplasmic biochemistry was proposed by Rudolph Peters in 1929 while the term (cytosquelette, in French) was first introduced by French embryologist Paul Wintrebert in 1931.

The eukaryotic cytoskeleton. Actin filaments are shown in red, microtubules in green, and the nuclei are in blue.



The Eukaryotic Cytoskeleton

Eukaryotic cells contain three main kinds of cytoskeletal filaments, which are microfilaments, intermediate filaments, and microtubules. The cytoskeleton provides the cell with structure and shape, and by excluding macromolecules from some of the cytosol it adds to the level of macromolecular crowding in this compartment. Cytoskeletal elements interact extensively and intimately with cellular membranes. A number of small molecule cytoskeletal drugs have been discovered that interact with actin and microtubules. These compounds have proven useful in studying the cytoskeleton and several have clinical applications.

Actin cytoskeleton of mouse embryo fibroblasts, stained with phalloidin.

Microfilaments (actin filaments)

These are the thinnest filaments of the cytoskeleton. They are composed of linear polymers of actin subunits, and generate force by elongation at one end of the filament coupled with shrinkage at the other, causing net movement of the intervening strand. They also act as tracks for the movement of myosin molecules that attach to the microfilament and "walk" along them. Actin structures are controlled by the Rho family of small GTP-binding proteins such as Rho itself for contractile acto-myosin filaments ("stress fibers"), Rac for lamellipodia and Cdc42 for filopodia.

Intermediate filaments
These filaments, averaging 10 nanometers in diameter, are more stable (strongly bound) than actin filaments, and heterogeneous constituents of the cytoskeleton. Like actin filaments, they function in the maintenance of cell-shape by bearing tension (microtubules, by contrast, resist compression. It may be useful to think of micro- and intermediate filaments as cables, and of microtubules as cellular support beams). Intermediate filaments organize the internal tridimensional structure of the cell, anchoring organelles and serving as structural components of the nuclear lamina and sarcomeres. They also participate in some cell-cell and cell-matrix junctions. Different intermediate filaments are: made of vimentins, being the common structural support of many cells. made of keratin, found in skin cells, hair and nails. neurofilaments of neural cells. made of lamin, giving structural support to the nuclear envelope.
Microscopy of keratin filaments inside cells.



Microtubules are hollow cylinders about 23nm in diameter (lumen = approximately 15nm in diameter), most commonly comprising 13 protofilaments which, in turn, are polymers of alpha and beta tubulin. They have a very dynamic behaviour, binding GTP for polymerization. They are commonly organized by the centrosome. In nine triplet sets (star-shaped), they form the centrioles, and in nine doublets oriented about two additional microtubules (wheel-shaped) they form cilia and flagella. The latter formation is commonly referred to as a "9+2" arrangement, where in each doublet is connected to another by the protein dynein. As both flagella and cilia are structural components of the cell, and are maintained by microtubules, they can be considered part of the cytoskeleton. They play key roles in: intracellular transport (associated with dyneins and kinesins, they transport organelles like mitochondria or vesicles). the axoneme of cilia and flagella. the mitotic spindle. synthesis of the cell wall in plants.

Microtubules in a gel fixated cell.

Cytoskeleton type [1] Diameter (nm) 6 10 double helix two anti-parallel helices/dimers, forming tetramers Structure Subunit examples

Microfilaments Intermediate filaments

actin vimentin (mesenchyme) glial fibrillary acidic protein (glial cells) neurofilament proteins (neuronal processes) keratins (epithelial cells) nuclear lamins



protofilaments, in turn consisting of tubulin subunits in complex - and -tubulin with stathmin

The prokaryotic cytoskeleton

The cytoskeleton was previously thought to be a feature only of eukaryotic cells, but homologues to all the major proteins of the eukaryotic cytoskeleton have recently been found in prokaryotes. Although the evolutionary relationships are so distant that they are not obvious from protein sequence comparisons alone, the similarity of their three-dimensional structures and similar functions in maintaining cell shape and polarity provides strong evidence that the eukaryotic and prokaryotic cytoskeletons are truly homologous. However, some structures in the bacterial cytoskeleton may have yet to be identified.



FtsZ was the first protein of the prokaryotic cytoskeleton to be identified. Like tubulin, FtsZ forms filaments in the presence of GTP, but these filaments do not group into tubules. During cell division, FtsZ is the first protein to move to the division site, and is essential for recruiting other proteins that synthesize the new cell wall between the dividing cells.

MreB and ParM

Prokaryotic actin-like proteins, such as MreB, are involved in the maintenance of cell shape. All non-spherical bacteria have genes encoding actin-like proteins, and these proteins form a helical network beneath the cell membrane that guides the proteins involved in cell wall biosynthesis. Some plasmids encode a partitioning system that involves an actin-like protein ParM. Filaments of ParM exhibit dynamic instability, and may partition plasmid DNA into the dividing daughter cells by a mechanism analogous to that used by microtubules during eukaryotic mitosis.

The bacterium Caulobacter crescentus contains a 3rd protein, crescentin, that is related to the intermediate filaments of eukaryotic cells. Crescentin is also involved in maintaining cell shape, such as helical and vibrioid forms of bacteria, but the mechanism by which it does this is currently unclear.

A fourth eukaryotic cytoskeletal element, microtrabeculae, was proposed by Keith Porter based on images obtained from high-voltage electron microscopy of whole cells in the 1970s. The images showed short, filamentous structures of unknown molecular composition associated with known cytoplasmic structures. Porter proposed that this microtrabecular structure represented a novel filamentous network distinct from microtubules, filamentous actin, or intermediate filaments. It is now generally accepted that microtrabeculae are nothing more than an artifact of certain types of fixation treatment, although we have yet to fully understand the complexity of the cell's cytoskeleton.

[1] Unless else specified in boxes, then ref is: Page 25

External links
Cytoskeleton, Cell Motility and Motors - The Virtual Library of Biochemistry and Cell Biology (http://www. Cytoskeleton database, clinical trials, recent literature, lab registry ... ( Animation of leukocyte adhesion ( swf&width=640&height=520) (Animation with some images of actin and microtubule assembly and dynamics.) and cell motility including videos Open access review article ( on the emergent complexity of the cytoskeleton (appeared in Advances in Physics, 2013)




Two mitochondria from mammalian lung tissue displaying their matrix and membranes as shown by electron microscopy

Cell biology

Components of a typical animal cell: 1. Nucleolus 2. Nucleus 3. Ribosome (little dots) 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus (or "Golgi body") 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytosol (fluid that contains organelles) 12. Lysosome 13. Centrosome 14. Cell membrane



Components of a typical mitochondrion 1 Outer membrane 1.1 Porin 2 Intermembrane space 2.1 Intracristal space 2.2 Peripheral space 3 Lamella 3.1 Inner membrane 3.11 Inner boundary membrane 3.12 Cristal membrane 3.2 Matrix 3.3 Crist 4 Mitochondrial DNA 5 Matrix granule 6 Ribosome 7 ATP synthase

The mitochondrion (plural mitochondria) is a membrane-enclosed structure found in most eukaryotic cells (the cells that make up plants, animals, fungi, and many other forms of life). Mitochondria range from 0.5 to 1.0micrometer (m) in diameter. These organelles are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. In addition to supplying cellular energy, mitochondria are involved in other tasks such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth. Mitochondria have been implicated in several human diseases, including mitochondrial disorders and cardiac dysfunction, and may play a role in the aging process. The word mitochondrion comes from the Greek , mitos, i.e. "thread", and , chondrion, i.e. "granule". Several characteristics make mitochondria unique. The number of mitochondria in a cell varies widely by organism and tissue type. Many cells have only a single mitochondrion, whereas others can contain several thousand mitochondria. The organelle is composed of compartments that carry out specialized functions. These compartments or regions include the outer membrane, the intermembrane space, the inner membrane, and the cristae and matrix. Mitochondrial proteins vary depending on the tissue and the species. In humans, 615 distinct types of proteins have been identified from cardiac mitochondria, whereas in rats, 940 proteins have been reported. The mitochondrial proteome is thought to be dynamically regulated. Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome. Further, its DNA shows substantial similarity to bacterial genomes.



The first observations of intracellular structures that probably represent mitochondria were published in the 1840s. Richard Altmann, in 1894, established them as cell organelles and called them "bioblasts". The term "mitochondria" itself was coined by Carl Benda in 1898. Leonor Michaelis discovered that Janus green can be used as a supravital stain for mitochondria in 1900. Friedrich Meves, in 1904, made the first recorded observation of mitochondria in plants (Nymphaea alba)[1] and in 1908, along with Claudius Regaud, suggested that they contain proteins and lipids. Benjamin F. Kingsbury, in 1912, first related them with cell respiration, but almost exclusively based on morphological observations. In 1913 particles from extracts of guinea-pig liver were linked to respiration by Otto Heinrich Warburg, which he called "grana". Warburg and Heinrich Otto Wieland, who had also postulated a similar particle mechanism, disagreed on the chemical nature of the respiration. It was not until 1925 when David Keilin discovered cytochromes that the respiratory chain was described. In 1939 experiments using minced muscle cells demonstrated that one oxygen atom can form two adenosine triphosphate molecules and in 1941 the concept of phosphate bonds being a form of energy in cellular metabolism was developed by Fritz Albert Lipmann. In the following years the mechanism behind cellular respiration was further elaborated, although its link to the mitochondria was not known. The introduction of tissue fractionation by Albert Claude allowed mitochondria to be isolated from other cell fractions and biochemical analysis to be conducted on them alone. In 1946 he concluded that cytochrome oxidase and other enzymes responsible for the respiratory chain were isolated to the mitchondria. Over time the fractionation method was tweaked, improving the quality of the mitochondria isolated and other elements of cell respiration were determined to occur in the mitochondria. The first high-resolution micrographs appeared in 1952, replacing the Janus Green stains as the preferred way of visualising the mitochondria. This led to a more detailed analysis of the structure of the mitochondria, including confirmation that they were surrounded by a membrane. It also showed a second membrane inside the mitochondria that folded up in ridges dividing up the inner chamber and that the size and shape of the mitochondria varied from cell to cell. The popular term "powerhouse of the cell" was coined by Philip Siekevitz in 1957. In 1967 it was discovered that mitochondria contained ribosomes. In 1968 methods were developed for mapping the mitochondrial genes, with the genetic and physical map of yeast mitochondria being completed in 1976.



Mitochondrion ultrastructure (interactive diagram) A mitochondrion has a double membrane; the inner one contains its chemiosmotic apparatus and has deep grooves which increase its surface area. While commonly depicted as an "orange sausage with a blob inside of it" (like it is here), mitochondria can take many shapes and their intermembrane space is quite thin.

A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins. The two membranes have different properties. Because of this double-membraned organization, there are five distinct parts to a mitochondrion. They are: 1. the outer mitochondrial membrane, 2. the intermembrane space (the space between the outer and inner membranes), 3. the inner mitochondrial membrane, 4. the cristae space (formed by infoldings of the inner membrane), and 5. the matrix (space within the inner membrane). Mitochondria stripped of their outer membrane are called mitoplasts.

Illustration depicting general mitochondrion structure

Outer membrane
The outer mitochondrial membrane, which encloses the entire organelle, has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane (about 1:1 by weight). It contains large numbers of integral proteins called porins. These porins form channels that allow molecules 5000Daltons or less in molecular weight to freely diffuse from one side of the membrane to the other. Larger proteins can enter the mitochondrion if a signaling sequence at their N-terminus binds to a large multisubunit protein called translocase of the outer membrane, which then actively moves them across the membrane. Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to certain cell death. The mitochondrial outer membrane can associate with the endoplasmic reticulum (ER) membrane, in a structure called MAM (mitochondria-associated ER-membrane). This is important in the ER-mitochondria calcium signaling and involved in the transfer of lipids between the ER and mitochondria.

Intermembrane space
The intermembrane space is the space between the outer membrane and the inner membrane. It is also known as perimitochondrial space. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol. However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the cytosol. One protein that is localized to the intermembrane space in this way is cytochrome c.



Inner membrane
The inner mitochondrial membrane contains proteins with five types of functions: 1. 2. 3. 4. 5. Those that perform the redox reactions of oxidative phosphorylation ATP synthase, which generates ATP in the matrix Specific transport proteins that regulate metabolite passage into and out of the matrix Protein import machinery. Mitochondria fusion and fission protein.

It contains more than 151 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1protein for 15phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion. In addition, the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in cow hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes. Cardiolipin contains four fatty acids rather than two, and may help to make the inner membrane impermeable. Unlike the outer membrane, the inner membrane doesn't contain porins, and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via Oxa1. In addition, there is a membrane potential across the inner membrane, formed by the action of the enzymes of the electron transport chain. Cristae The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. For typical liver mitochondria, the area of the inner membrane is about five times as large as the outer membrane. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. These folds are studded with small round bodies known as F1 particles or oxysomes. These are not simple random folds but rather invaginations of the inner membrane, which can affect overall chemiosmotic function.

Cross-sectional image of cristae in rat liver mitochondrion to demonstrate the likely 3D structure and relationship to the inner membrane

One recent mathematical modeling study has suggested that the optical properties of the cristae in filamentous mitochondria may affect the generation and propagation of light within the tissue.

The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total protein in a mitochondrion. The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle. Mitochondria have their own genetic material, and the machinery to manufacture their own RNAs and proteins (see: protein biosynthesis). A published human mitochondrial DNA sequence revealed 16,569base pairs encoding 37 total genes: 22tRNA, 2 rRNA, and 13peptide genes. The 13 mitochondrial peptides in humans are integrated into the

Mitochondrion inner mitochondrial membrane, along with proteins encoded by genes that reside in the host cell's nucleus.


Mitochondria-associated ER membrane (MAM)

The mitochondria-associated ER membrane (MAM) is another structural element that is increasingly recognized for its critical role in cellular physiology and homeostasis. Once considered a technical snag in cell fractionation techniques, the alleged ER vesicle contaminants that invariably appeared in the mitochondrial fraction have been re-identified as membranous structures derived from the MAMthe interface between mitochondria and the ER. Physical coupling between these two organelles had previously been observed in electron micrographs and has more recently been probed with fluorescence microscopy. Such studies estimate that at the MAM, which may comprise up to 20% of the mitochondrial outer membrane, the ER and mitochondria are separated by a mere 10-25nm and held together by protein tethering complexes. Purified MAM from subcellular fractionation has shown to be enriched in enzymes involved in phospholipid exchange, in addition to channels associated with Ca2+ signaling. These hints of a prominent role for the MAM in the regulation of cellular lipid stores and signal transduction have been borne out, with significant implications for mitochondrial-associated cellular phenomena, as discussed below. Not only has the MAM provided insight into the mechanistic basis underlying such physiological processes as intrinsic apoptosis and the propagation of calcium signaling, but it also favors a more refined view of the mitochondria. Though often seen as static, isolated powerhouses hijacked for cellular metabolism through an ancient endosymbiotic event, the evolution of the MAM underscores the extent to which mitochondria have been integrated into overall cellular physiology, with intimate physical and functional coupling to the endomembrane system. Phospholipid transfer The MAM is enriched in enzymes involved in lipid biosynthesis, such as phosphatidylserine synthase on the ER face and phosphatidylserine decarboxylase on the mitochondrial face. Because mitochondria are dynamic organelles constantly undergoing fission and fusion events, they require a constant and well-regulated supply of phospholipids for membrane integrity. But mitochondria are not only a destination for the phospholipids they finish synthesis of; rather, this organelle also plays a role in inter-organelle trafficking of the intermediates and products of phospholipid biosynthetic pathways, ceramide and cholesterol metabolism, and glycosphingolipid anabolism. Such trafficking capacity depends on the MAM, which has been shown to facilitate transfer of lipid intermediates between organelles. In contrast to the standard vesicular mechanism of lipid transfer, evidence indicates that the physical proximity of the ER and mitochondrial membranes at the MAM allows for lipid flipping between opposed bilayers. Despite this unusual and seemingly energetically unfavorable mechanism, such transport does not require ATP. Instead, in yeast, it has been shown to be dependent on a multiprotein tethering structure termed the ER-mitochondria encounter structure, or ERMES, although it remains unclear whether this structure directly mediates lipid transfer or is required to keep the membranes in sufficiently close proximity to lower the energy barrier for lipid flipping. The MAM may also be part of the secretory pathway, in addition to its role in intracellular lipid trafficking. In particular, the MAM appears to be an intermediate destination between the rough ER and the Golgi in the pathway that leads to very-low-density lipoprotein, or VLDL, assembly and secretion. The MAM thus serves as a critical metabolic and trafficking hub in lipid metabolism.

Mitochondrion Calcium signaling A critical role for the ER in calcium signaling was acknowledged before such a role for the mitochondria was widely accepted, in part because the low affinity of Ca2+ channels localized to the outer mitochondrial membrane seemed to fly in the face of this organelles purported responsiveness to changes in intracellular Ca2+ flux. But the presence of the MAM resolves this apparent contradiction: the close physical association between the two organelles results in Ca2+ microdomains at contact points that facilitate efficient Ca2+ transmission from the ER to the mitochondria. Transmission occurs in response to so-called Ca2+ puffs generated by spontaneous clustering and activation of IP3R, a canonical ER membrane Ca2+ channel. The fate of these puffsin particular, whether they remain restricted to isolated locales or integrated into Ca2+ waves for propagation throughout the cellis determined in large part by MAM dynamics. Although reuptake of Ca2+ by the ER (concomitant with its release) modulates the intensity of the puffs, thus insulating mitochondria to a certain degree from high Ca2+ exposure, the MAM often serves as a firewall that essentially buffers Ca2+ puffs by acting as a sink into which free ions released into the cytosol can be funneled. This Ca2+ tunneling occurs through the low-affinity Ca2+ receptor VDAC1, which recently has been shown to be physically tethered to the IP3R clusters on the ER membrane and enriched at the MAM. The ability of mitochondria to serve as a Ca2+ sink is a result of the electrochemical gradient generated during oxidative phosphorylation, which makes tunneling of the cation an exergonic process. But transmission of Ca2+ is not unidirectional; rather, it is a two-way street. The properties of the Ca2+ pump SERCA and the channel IP3R present on the ER membrane facilitate feedback regulation coordinated by MAM function. In particular, clearance of Ca2+ by the MAM allows for spatio-temporal patterning of Ca2+ signaling because Ca2+ alters IP3R activity in a biphasic manner. SERCA is likewise affected by mitochondrial feedback: uptake of Ca2+ by the MAM stimulates ATP production, thus providing energy that enables SERCA to reload the ER with Ca2+ for continued Ca2+ efflux at the MAM. Thus, the MAM is not a passive buffer for Ca2+ puffs; rather it helps modulate further Ca2+ signaling through feedback loops that affect ER dynamics. Regulating ER release of Ca2+ at the MAM is especially critical because only a certain window of Ca2+ uptake sustains the mitochondria, and consequently the cell, at homeostasis. Sufficient intraorganelle Ca2+ signaling is required to stimulate metabolism by activating dehydrogenase enzymes critical to flux through the citric acid cycle. However, once Ca2+ signaling in the mitochondria passes a certain threshold, it stimulates the intrinsic pathway of apoptosis in part by collapsing the mitochondrial membrane potential required for metabolism. Studies examining the role of pro- and anti-apoptotic factors support this model; for example, the anti-apoptotic factor Bcl-2 has been shown to interact with IP3Rs to reduce Ca2+ filling of the ER, leading to reduced efflux at the MAM and preventing collapse of the mitochondrial membrane potential post-apoptotic stimuli. Given the need for such fine regulation of Ca2+ signaling, it is perhaps unsurprising that dysregulated mitochondrial Ca2+ has been implicated in several neurodegenerative diseases, while the catalogue of tumor suppressors includes a few that are enriched at the MAM. Molecular basis for tethering Recent advances in the identification of the tethers between the mitochondrial and ER membranes suggest that the scaffolding function of the molecular elements involved is secondary to other, non-structural functions. In yeast, ERMES, a multiprotein complex of interacting ER- and mitochondrial-resident membrane proteins, is required for lipid transfer at the MAM and exemplifies this principle. One of its components, for example, is also a constituent of the protein complex required for insertion of transmembrane beta-barrel proteins into the lipid bilayer. However, a homologue of the ERMES complex has not been identified yet in mammalian cells. Other proteins implicated in scaffolding likewise have functions independent of structural tethering at the MAM; for example, ER-resident and mitochondrial-resident mitofusins form heterocomplexes that regulate the number of inter-organelle contact sites, although mitofusins were first identified for their role in fission and fusion events between individual mitochondria. Glucose-related protein 75 (grp75) is another dual-function protein. In addition to the matrix pool of grp75, a portion


Mitochondrion serves as a chaperone that physically links the mitochondrial and ER Ca2+ channels VDAC and IP3R for efficient Ca2+ transmission at the MAM. Another potential tether is Sigma-1R, a non-opioid receptor whose stabilization of ER-resident IP3R may preserve communication at the MAM during the metabolic stress response. Perspective The MAM is a critical signaling, metabolic, and trafficking hub in the cell that allows for the integration of ER and mitochondrial physiology. Coupling between these organelles is not simply structural but functional as well and critical for overall cellular physiology and homeostasis. The MAM thus offers a perspective on mitochondria that diverges from the traditional view of this organelle as a static, isolated unit appropriated for its metabolic capacity by the cell. Instead, this mitochondrial-ER interface emphasizes the integration of the mitochondria, the product of an endosymbiotic event, into diverse cellular processes.
Model of the yeast multimeric tethering complex, ERMES


Organization and distribution

Mitochondria are found in nearly all eukaryotes.[2] They vary in number and location according to cell type. A single mitochondrion is often found in unicellular organisms. Conversely, numerous mitochondria are found in human liver cells, with about 10002000 mitochondria per cell, making up 1/5 of the cell volume. The mitochondrial content of otherwise similar cells can vary substantially in size and membrane potential, with differences arising from sources including uneven partitioning at cell divisions, leading to extrinsic differences in ATP levels and downstream cellular processes. The mitochondria can be found nestled between myofibrils of muscle or wrapped around the sperm flagellum. Often they form a complex 3D branching network inside the cell with the cytoskeleton. The association with the cytoskeleton determines mitochondrial shape, which can affect the function as well. Recent evidence suggests that vimentin, one of the components of the cytoskeleton, is critical to the association with the cytoskeleton.

The most prominent roles of mitochondria are to produce the energy currency of the cell, ATP (i.e., phosphorylation of ADP), through respiration, and to regulate cellular metabolism. The central set of reactions involved in ATP production are collectively known as the citric acid cycle, or the Krebs Cycle. However, the mitochondrion has many other functions in addition to the production of ATP.

Energy conversion
A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task. This is done by oxidizing the major products of glucose, pyruvate, and NADH, which are produced in the cytosol. This process of cellular respiration, also known as aerobic respiration, is dependent on the presence of oxygen. When oxygen is limited, the glycolytic products will be metabolized by anaerobic fermentation, a process that is independent of the mitochondria. The production of ATP from glucose has an approximately 13-times higher yield during aerobic respiration compared to fermentation. Recently it has been shown that plant mitochondria can produce a limited amount of ATP without oxygen by using the alternate substrate

Mitochondrion nitrite. Pyruvate and the citric acid cycle Each pyruvate molecule produced by glycolysis is actively transported across the inner mitochondrial membrane, and into the matrix where it is oxidized and combined with coenzyme A to form CO2, acetyl-CoA, and NADH. The acetyl-CoA is the primary substrate to enter the citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or Krebs cycle. The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane as part of Complex II. The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of NADH and one molecule of FADH2) that are a source of electrons for the electron transport chain, and a molecule of GTP (that is readily converted to an ATP). NADH and FADH2: the electron transport chain The redox energy from NADH and FADH2 is transferred to oxygen (O2) in several steps via the electron transport chain. These energy-rich molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by glycolysis. Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electron transport chain using a glycerol phosphate shuttle. Diagram of the electron transport chain in the mitonchondrial intermembrane space Protein complexes in the inner membrane (NADH dehydrogenase (ubiquinone), cytochrome c reductase, and cytochrome c oxidase) perform the transfer and the incremental release of energy is used to pump protons (H+) into the intermembrane space. This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide. This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process. As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. The protons can return to the matrix through the ATP synthase complex, and their potential energy is used to synthesize ATP from ADP and inorganic phosphate (Pi). This process is called chemiosmosis, and was first described by Peter Mitchell who was awarded the 1978 Nobel Prize in Chemistry for his work. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase. Heat production Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process is known as proton leak or mitochondrial uncoupling and is due to the facilitated diffusion of protons into the matrix. The process results in the unharnessed potential energy of the proton electrochemical gradient being released as heat. The process is mediated by a proton channel called thermogenin, or UCP1. Thermogenin is a 33kDa protein first discovered in 1973. Thermogenin is primarily found in brown adipose tissue, or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue is found in mammals, and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age.




Storage of calcium ions

The concentrations of free calcium in the cell can regulate an array of reactions and is important for signal transduction in the cell. Mitochondria can transiently store calcium, a contributing process for the cell's homeostasis of calcium. In fact, their ability to rapidly take in calcium for later release makes them very good "cytosolic buffers" for calcium.[3] The endoplasmic reticulum (ER) is the most significant storage site of Mitochondria (M) within a chondrocyte stained for calcium as shown by electron calcium, and there is a significant interplay microscopy between the mitochondrion and ER with regard to calcium. The calcium is taken up into the matrix by a calcium uniporter on the inner mitochondrial membrane. It is primarily driven by the mitochondrial membrane potential. Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-induced-calcium-release" pathways. This can initiate calcium spikes or calcium waves with large changes in the membrane potential. These can activate a series of second messenger system proteins that can coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells. Ca2+ influx to the mitochondrial matrix has recently been implicated as a mechanism to regulate respiratory bioenergetics by allowing the electrochemical potential across the membrane to transiently "pulse" from -dominated to pH-dominated, facilitating a reduction of oxidative stress.In neurons, concominant increases in cytosolic and mitochondrial calcium act to synchronize neuronal activity with mitochondrial energy metabolism. Mitochondrial matrix calcium levels can reach the tens of micromolar levels, which is necessary for the activation of isocitrate dehydrogenase, one of the key regulatory enzymes of the Kreb's cycle.

Additional functions
Mitochondria play a central role in many other metabolic tasks, such as: Signaling through mitochondrial reactive oxygen species Regulation of the membrane potential Apoptosis-programmed cell death Calcium signaling (including calcium-evoked apoptosis)

Regulation of cellular metabolism Certain heme synthesis reactions (see also: porphyrin) Steroid synthesis. Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in mitochondrial diseases.



Cellular proliferation regulation

The relationship between cellular proliferation and mitochondria has been investigated using cervical cancer Hela cells. Tumor cells require an ample amount of ATP (Adenosine triphosphate) in order to synthesize bioactive compounds such as lipids, proteins, and nucleotides for rapid cell proliferation. The majority of ATP in tumor cells is generated via the Oxidative Phosphorylation pathway (OxPhos). Interference with OxPhos have shown to cause cell cycle arrest suggesting that mitochondria plays a role in cell proliferation. Mitochondrial ATP production is also vital for cell division in addition to other basic functions in the cell including the regulation of cell volume, solute concentration, and cellular architecture. ATP levels differ at various stages of the cell cycle suggesting that there is a relationship between the abundance of ATP and the cell's ability to enter a new cell cycle. ATPs role in the basic functions of the cell make the cell cycle sensitive to changes in the availability of mitochondrial derived ATP. The variation in ATP levels at different stages of the cell cycle support the hypothesis that mitochondria plays an important role in cell cycle regulation. Although the specific mechanisms between mitochondria and the cell cycle regulation is not well understood, studies have shown that low energy cell cycle checkpoints monitor the energy capability before committing to another round of cell division.

There are two hypotheses about the origin of mitochondria: endosymbiotic and autogenous. The endosymbiotic hypothesis suggests mitochondria were originally prokaryotic cells, capable of implementing oxidative mechanisms that were not possible to eukaryotic cells; they became endosymbionts living inside the eukaryote. In the autogenous hypothesis, mitochondria were born by splitting off a portion of DNA from the nucleus of the eukaryotic cell at the time of divergence with the prokaryotes; this DNA portion would have been enclosed by membranes, which could not be crossed by proteins. Since mitochondria have many features in common with bacteria, the most accredited theory at present is endosymbiosis.[4] A mitochondrion contains DNA, which is organized as several copies of a single, circular chromosome. This mitochondrial chromosome contains genes for redox proteins such as those of the respiratory chain. The CoRR hypothesis proposes that this co-location is required for redox regulation. The mitochondrial genome codes for some RNAs of ribosomes, and the twenty-two tRNAs necessary for the translation of messenger RNAs into protein. The circular structure is also found in prokaryotes. The proto-mitochondrion was probably closely related to the rickettsia. However, the exact relationship of the ancestor of mitochondria to the alpha-proteobacteria and whether the mitochondrion was formed at the same time or after the nucleus, remains controversial. A recent study by researchers of the University of Hawaii at Mnoa and the Oregon State University indicates that the SAR11 clade of bacteria shares a relatively recent common ancestor with the mitochondria existing in most eukaryotic cells.
Phylogeny of Rickettsiales



Other alphaproteobacteria Rhodospirillales, Sphingomonadales, Rhodobacteraceae, Rhizobiales, etc.

SAR11 clade Pelagibacter ubique


Ehrlichia Rickettsiales Anaplasmataceae Anaplasma





Robust phylogeny of Rickettsiales from Williams et al. (2007)

The ribosomes coded for by the mitochondrial DNA are similar to those from bacteria in size and structure. They closely resemble the bacterial 70S ribosome and not the 80S cytoplasmic ribosomes, which are coded for by nuclear DNA. The endosymbiotic relationship of mitochondria with their host cells was popularized by Lynn Margulis. The endosymbiotic hypothesis suggests that mitochondria descended from bacteria that somehow survived endocytosis by another cell, and became incorporated into the cytoplasm. The ability of these bacteria to conduct respiration in host cells that had relied on glycolysis and fermentation would have provided a considerable evolutionary advantage. This symbiotic relationship probably developed 1.7 to 2 billion years ago. A few groups of unicellular eukaryotes lack mitochondria: the microsporidians, metamonads, and archamoebae. These groups appear as the most primitive eukaryotes on phylogenetic trees constructed using rRNA information, which once suggested that they appeared before the origin of mitochondria. However, this is now known to be an artifact of long-branch attractionthey are derived groups and retain genes or organelles derived from mitochondria (e.g., mitosomes and hydrogenosomes).



The human mitochondrial genome is a circular DNA molecule of about 16kilobases. It encodes 37 genes: 13 for subunits of respiratory complexes I, III, IV and V, 22 for mitochondrial tRNA (for the 20 standard amino acids, plus an extra gene for leucine and serine), and 2 for rRNA. One mitochondrion can contain two to ten copies of its DNA. As in prokaryotes, there is a very high proportion of coding DNA and an absence of repeats. Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield Mitochondrial DNA. mature mRNAs. Not all proteins necessary for mitochondrial function are encoded by the mitochondrial genome; most are coded by genes in the cell nucleus and the corresponding proteins are imported into the mitochondrion. The exact number of genes encoded by the nucleus and the mitochondrial genome differs between species. Most mitochondrial genomes are circular, although exceptions have been reported. In general, mitochondrial DNA lacks introns, as is the case in the human mitochondrial genome; however, introns have been observed in some eukaryotic mitochondrial DNA, such as that of yeast and protists, including Dictyostelium discoideum. In animals the mitochondrial genome is typically a single circular chromosome that is approximately 16 kb long and has 37 genes. The genes, while highly conserved, may vary in location. Curiously, this pattern is not found in the human body louse (Pediculus humanus). Instead this mitochondrial genome is arranged in 18 minicircular chromosomes, each of which is 34 kb long and has one to three genes. This pattern is also found in other sucking lice, but not in chewing lice. Recombination has been shown to occur between the minichromosomes. The reason for this difference is not known. While slight variations on the standard code had been predicted earlier,[5] none was discovered until 1979, when researchers studying human mitochondrial genes determined that they used an alternative code. Although, the mitochondria of many other eukaryotes, including most plants, use the standard code.[6] Many slight variants have been discovered since,[7] including various alternative mitochondrial codes. Further, the AUA, AUC, and AUU codons are all allowable start codons.

Exceptions to the universal genetic code (UGC) in mitochondria

Organism Mammals Invertebrates Fungi Codon Standard Mitochondria Stopcodon Serine Threonine Methionine

AGA,AGG Arginine AGA, AGG Arginine CUA Leucine Isoleucine

All of the above AUA UGA

Stop codon Tryptophan

Some of these differences should be regarded as pseudo-changes in the genetic code due to the phenomenon of RNA editing, which is common in mitochondria. In higher plants, it was thought that CGG encoded for tryptophan and not arginine; however, the codon in the processed RNA was discovered to be the UGG codon, consistent with the universal genetic code for tryptophan. Of note, the arthropod mitochondrial genetic code has undergone parallel evolution within a phylum, with some organisms uniquely translating AGG to lysine. Mitochondrial genomes have far fewer genes than the bacteria from which they are thought to be descended. Although some have been lost altogether, many have been transferred to the nucleus, such as the respiratory complex

Mitochondrion II protein subunits. This is thought to be relatively common over evolutionary time. A few organisms, such as the Cryptosporidium, actually have mitochondria that lack any DNA, presumably because all their genes have been lost or transferred. In Cryptosporidium, the mitochondria have an altered ATP generation system that renders the parasite resistant to many classical mitochondrial inhibitors such as cyanide, azide, and atovaquone.


Replication and inheritance

Mitochondria divide by binary fission, similar to bacterial cell division. The regulation of this division differs between eukaryotes. In many single-celled eukaryotes, their growth and division is linked to the cell cycle. For example, a single mitochondrion may divide synchronously with the nucleus. This division and segregation process must be tightly controlled so that each daughter cell receives at least one mitochondrion. In other eukaryotes (in mammals for example), mitochondria may replicate their DNA and divide mainly in response to the energy needs of the cell, rather than in phase with the cell cycle. When the energy needs of a cell are high, mitochondria grow and divide. When the energy use is low, mitochondria are destroyed or become inactive. In such examples, and in contrast to the situation in many single celled eukaryotes, mitochondria are apparently randomly distributed to the daughter cells during the division of the cytoplasm. Understanding of mitochondrial dynamics, which is described as the balance between mitochondrial fusion and fission, has revealed that functional and structural alterations in mitochondrial morphology are important factors in pathologies associated with several disease conditions. An individual's mitochondrial genes are not inherited by the same mechanism as nuclear genes. Typically, the mitochondria are inherited from one parent only. In humans, when an egg cell is fertilized by a sperm, the egg nucleus and sperm nucleus each contribute equally to the genetic makeup of the zygote nucleus. In contrast, the mitochondria, and therefore the mitochondrial DNA, usually come from the egg only. The sperm's mitochondria enter the egg but do not contribute genetic information to the embryo.[8] Instead, paternal mitochondria are marked with ubiquitin to select them for later destruction inside the embryo.[9] The egg cell contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. Mitochondria are, therefore, in most cases inherited only from mothers, a pattern known as maternal inheritance. This mode is seen in most organisms including the majority of animals. However, mitochondria in some species can sometimes be inherited paternally. This is the norm among certain coniferous plants, although not in pine trees and yew trees. For Mytilidae mussels paternal inheritance only occurs within males of the species.[10] It has been suggested that it occurs at a very low level in humans. There is a recent suggestion mitochondria that shorten male lifespan stay in the system because mitochondria are inherited only through the mother. By contrast natural selection weeds out mitochondria that reduce female survival as such mitochondria are less likely to be passed on to the next generation. Therefore it is suggested human females and female animals tend to live longer than males. The authors claim this is a partial explanation.[11] Uniparental inheritance leads to little opportunity for genetic recombination between different lineages of mitochondria, although a single mitochondrion can contain 210 copies of its DNA. For this reason, mitochondrial DNA usually is thought to reproduce by binary fission. What recombination does take place maintains genetic integrity rather than maintaining diversity. However, there are studies showing evidence of recombination in mitochondrial DNA. It is clear that the enzymes necessary for recombination are present in mammalian cells. Further, evidence suggests that animal mitochondria can undergo recombination. The data are a bit more controversial in humans, although indirect evidence of recombination exists. If recombination does not occur, the whole mitochondrial DNA sequence represents a single haplotype, which makes it useful for studying the evolutionary history of populations.



Population genetic studies

The near-absence of genetic recombination in mitochondrial DNA makes it a useful source of information for scientists involved in population genetics and evolutionary biology. Because all the mitochondrial DNA is inherited as a single unit, or haplotype, the relationships between mitochondrial DNA from different individuals can be represented as a gene tree. Patterns in these gene trees can be used to infer the evolutionary history of populations. The classic example of this is in human evolutionary genetics, where the molecular clock can be used to provide a recent date for mitochondrial Eve. This is often interpreted as strong support for a recent modern human expansion out of Africa. Another human example is the sequencing of mitochondrial DNA from Neanderthal bones. The relatively large evolutionary distance between the mitochondrial DNA sequences of Neanderthals and living humans has been interpreted as evidence for lack of interbreeding between Neanderthals and anatomically modern humans. However, mitochondrial DNA reflects the history of only females in a population and so may not represent the history of the population as a whole. This can be partially overcome by the use of paternal genetic sequences, such as the non-recombining region of the Y-chromosome. In a broader sense, only studies that also include nuclear DNA can provide a comprehensive evolutionary history of a population.

Dysfunction and disease

Mitochondrial diseases
Damage and subsequent dysfunction in mitochondria is an important factor in a range of human diseases due to their influence in cell metabolism. Mitochondrial disorders often present themselves as neurological disorders, but can manifest as myopathy, diabetes, multiple endocrinopathy, or a variety of other systemic manifestations. Diseases caused by mutation in the mtDNA include Kearns-Sayre syndrome, MELAS syndrome and Leber's hereditary optic neuropathy. In the vast majority of cases, these diseases are transmitted by a female to her children, as the zygote derives its mitochondria and hence its mtDNA from the ovum. Diseases such as Kearns-Sayre syndrome, Pearson's syndrome, and progressive external ophthalmoplegia are thought to be due to large-scale mtDNA rearrangements, whereas other diseases such as MELAS syndrome, Leber's hereditary optic neuropathy, myoclonic epilepsy with ragged red fibers (MERRF), and others are due to point mutations in mtDNA. In other diseases, defects in nuclear genes lead to dysfunction of mitochondrial proteins. This is the case in Friedreich's ataxia, hereditary spastic paraplegia, and Wilson's disease. These diseases are inherited in a dominance relationship, as applies to most other genetic diseases. A variety of disorders can be caused by nuclear mutations of oxidative phosphorylation enzymes, such as coenzyme Q10 deficiency and Barth syndrome. Environmental influences may interact with hereditary predispositions and cause mitochondrial disease. For example, there may be a link between pesticide exposure and the later onset of Parkinson's disease. Other pathologies with etiology involving mitochondrial dysfunction include schizophrenia, bipolar disorder, dementia, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, cardiovascular disease, retinitis pigmentosa, and diabetes mellitus. Mitochondria-mediated oxidative stress plays a role in cardiomyopathy in Type 2 diabetics. Increased fatty acid delivery to the heart increases fatty acid uptake by cardiomyocytes, resulting in increased fatty acid oxidation in these cells. This process increases the reducing equivalents available to the electron transport chain of the mitochondria, ultimately increasing reactive oxygen species (ROS) production. ROS increases uncoupling proteins (UCPs) and potentiate proton leakage through the adenine nucleotide translocator (ANT), the combination of which uncouples the mitochondria. Uncoupling then increases oxygen consumption by the mitochondria, compounding the increase in fatty acid oxiation. This creates a vicious cycle of uncoupling; furthermore, even though oxygen consumption increases, ATP synthesis does not increase proportionally because the mitochondria is uncoupled. Less ATP availability ultimately results in an energy deficit presenting as reduced cardiac efficiency and contractile dysfunction. To compound the problem, impaired sarcoplasmic reticulum calcium release and reduced mitochondrial reuptake limits peak cytosolic levels of the important signaling ion during muscle contraction. The decreased

Mitochondrion intra-mitochondrial calcium concentration increases dehydrogenase activation and ATP synthesis. So in addition to lower ATP synthesis due to fatty acid oxidation, ATP synthesis is impaired by poor calcium signaling as well, causing cardiac problems for diabetics.


Possible relationships to aging

Given the role of mitochondria as the cell's powerhouse, there may be some leakage of the high-energy electrons in the respiratory chain to form reactive oxygen species. This was thought to result in significant oxidative stress in the mitochondria with high mutation rates of mitochondrial DNA (mtDNA). Hypothesized links between aging and oxidative stress are not new and were proposed over 60 years ago, which was later refined into the mitochondrial free radical theory of aging. A vicious cycle was thought to occur, as oxidative stress leads to mitochondrial DNA mutations, which can lead to enzymatic abnormalities and further oxidative stress. However, recent measurements of the rate of accumulation of mutation observed in mitochondrial DNA[12] were estimated to be 1 mutation every 7884 years (10^-7 to 10^-9 per base per year, dating back to the most recent common ancestor of humans and apes), consistent with other estimates of mutation rates of autosomal dna ( 10^-8 per base per generation[13]) A number of changes can occur to mitochondria during the aging process. Tissues from elderly patients show a decrease in enzymatic activity of the proteins of the respiratory chain. However, mutated mtDNA can only be found in about 0.2% of very old cells.[14] Large deletions in the mitochondrial genome have been hypothesized to lead to high levels of oxidative stress and neuronal death in Parkinson's disease. However, there is much debate over whether mitochondrial changes are causes of aging or merely characteristics of aging. One notable study in mice demonstrated shortened lifespan but no increase in reactive oxygen species despite increasing mitochondrial DNA mutations. However, it has to be noted that aging non-mutant mice do not seem to accumulate a great number of mutations in mitochondrial DNA imposing a cloud of doubt on the involvement of mitochondrial DNA mutations in "natural" aging. As a result, the exact relationships between mitochondria, oxidative stress, and aging have not yet been settled.

In popular culture
In Madeleine L'Engle's A Wind in the Door, the Farandolae are fictional creatures that live inside mitochondria, and do circular "dances" around their "trees of origin". In the Japanese novel Parasite Eve and the associated manga and video games, various characters are able to manipulate the energies contained within their mitochondria, generating a wide array of effects on other living creatures. In the 2012 feature film The Bourne Legacy, the green pills taken by Aaron Cross (Jeremy Renner) contain a virus that implants itself in the user's cells, increasing mitochondrial output.

This article incorporatespublic domain material from the NCBI document "Science Primer" [15].
[1] Ernster's citation is wrong, correct citation is , cited in Meves' 1908 paper and in , with confirmation of Nymphaea alba [2] The eukaryote Giardia lamblia, for example, does not contain mitochondria, but does have a mitochondiral-like gene, suggesting that it once included either mitochondria or an endosymbiotic progenitor of it [3] Brighton, Carl T. and Robert M. Hunt (1978): "The role of mitochondria in growth plate calcification as demonstrated in a rachitic model", Journal of Bone and Joint Surgery, 60-A: 630-639. [4] William F. Martin and Mikls Mller "Origin of mitochondria and hydrogenosomes", Springer Verlag, Heidelberg 2007. [5] Crick, F. H. C. and Orgel, L. E. (1973) "Directed panspermia." Icarus 19:341-346. p. 344: "It is a little surprising that organisms with somewhat different codes do not coexist." (Further discussion at (http:/ / www. talkorigins. org/ faqs/ comdesc/ section1. html) ) [6] NCBI "Mitochondrial Genetic Code in Taxonomy Tree" (http:/ / www. ncbi. nlm. nih. gov/ Taxonomy/ Utils/ wprintgc. cgi) [7] NCBI: "The Genetic Codes", Compiled by Andrzej (Anjay) Elzanowski and Jim Ostell (http:/ / 130. 14. 29. 110/ Taxonomy/ Utils/ wprintgc. cgi?mode=c)

[8] Kimball, J.W. (2006) "Sexual Reproduction in Humans: Copulation and Fertilization," (http:/ / home. comcast. net/ ~john. kimball1/ BiologyPages/ S/ Sexual_Reproduction. html#Copulation_and_Fertilization) Kimball's Biology Pages (based on Biology, 6th ed., 1996)] [9] Discussed in Science News (http:/ / www. sciencenews. org/ 20000101/ fob3. asp). [10] Male and Female Mitochondrial DNA Lineages in the Blue Mussel (Mytilus edulis) Species Group (http:/ / mbe. library. arizona. edu/ data/ 1995/ 1205/ 3stew. pdf) by Donald T. Stewart, Carlos Saavedra, Rebecca R. Stanwood, Amy 0. Ball, and Eleftherios Zouros [11] Fruit flies offer DNA clue to why women live longer (http:/ / www. bbc. co. uk/ news/ health-19093442) [12] Soares et al, Correcting for Purifying Selection: An Improved Human Mitochondrial Molecular Clock (http:/ / www. ncbi. nlm. nih. gov/ pmc/ articles/ PMC2694979/ ?tool=pubmed) Am J Hum Genet. 2009 June 12; 84(6) 740759. [13] Michael W. Nachman and Susan L. Crowell Estimate of the Mutation Rate per Nucleotide in Humans (http:/ / www. genetics. org/ content/ 156/ 1/ 297. full) Genetics, Vol. 156, 297-304, September 2000 [14] de Grey, Aubrey (Fall 2004). " Mitochondrial Mutations in Mammalian Aging: An Over-Hasty About-Turn? (http:/ / www. mprize. com/ files/ sens/ polg-PP. pdf)" Rejuvenation Res. 7 (3) 1714. . PMID 15588517. [15] http:/ / www. ncbi. nlm. nih. gov/ About/ primer/ index. html


External links ( - The mitochondrial disease database. Mitochondria Atlas ( at University of Mainz Mitochondria Research Portal ( at Mitochondria: Architecture dictates function ( at Mitochondria links ( at University of Alabama MIP ( Mitochondrial Physiology Society 3D structures of proteins from inner mitochondrial membrane ( php?localization=Mitochondrial inner membrane) at University of Michigan 3D structures of proteins associated with outer mitochondrial membrane ( localization.php?localization=Mitochondrial outer membrane) at University of Michigan Mitochondrial Protein Partnership ( at University of Wisconsin MitoMiner - A mitochondrial proteomics database ( at MRC Mitochondrial Biology Unit Mitochondrion - Cell Centered Database ( keyword=mitochondrion&Submit=Go&event=display&start=1) Mitochondrion Reconstructed by Electron Tomography ( at San Diego State University Video Clip of Rat-liver Mitochondrion from Cryo-electron Tomography ( electron/cryomito_dis2.html)



A vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal[1] and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain cases they may contain solids which have been engulfed. Vacuoles are formed by the fusion of multiple membrane vesicles and are effectively just larger forms of these.[2] The organelle has no basic shape or size; its structure varies according to the needs of the cell.
Plant cell structure

The function and significance of vacuoles varies greatly according to the type of cell in which they are present, having much greater prominence in the cells of plants, fungi and certain protists than those of animals and bacteria. In general, the functions of the vacuole include: Isolating materials that might be harmful or a threat to the cell Containing waste products Containing water in plant cells Maintaining internal hydrostatic pressure or turgor within the cell Maintaining an acidic internal pH
Animal cell structure

Containing small molecules Exporting unwanted substances from the cell Allows plants to support structures such as leaves and flowers due to the pressure of the central vacuole In seeds, stored proteins needed for germination are kept in 'protein bodies', which are modified vacuoles.[3]

Vacuoles also play a major role in autophagy, maintaining a balance between biogenesis (production) and degradation (or turnover), of many substances and cell structures in certain organisms. They also aid in the lysis and recycling of misfolded proteins that have begun to build up within the cell. Thomas Boller [4] and others proposed that the vacuole participates in the destruction of invading bacteria and Robert B Mellor proposed organ-specific forms have a role in 'housing' symbiotic bacteria. In protists, vacuoles have the additional function of storing food which has been absorbed by the organism and assisting in the digestive and waste management process for the cell. The vacuole probably evolved several times independently, even within the Viridiplantae.[5]



Large vacuoles are found in three genera of filamentous sulfur bacteria, the Thioploca, Beggiatoa and Thiomargarita. The cytosol is extremely reduced in these genera and the vacuole can occupy between 4098% of the cell. The vacuole contains high concentrations of nitrate ions and is therefore thought to be a storage organelle. Gas vacuoles, which are freely permeable to gas, are present in some species of Cyanobacteria. They allow the bacteria to control their buoyancy.

Most mature plant cells have one large vacuole that typically occupies more than 30% of the cell's volume, and that can occupy as much as 80% of the volume for certain cell types and conditions.[6] Strands of cytoplasm often run through the vacuole. A vacuole is surrounded by a membrane called the tonoplast (word origin: Gk tn(os) + -o-, meaning stretching, tension, tone + comb. form repr. Gk plasts formed, molded). Also called the vacuolar membrane, the tonoplast is the cytoplasmic membrane surrounding a vacuole, separating the vacuolar contents from the cell's cytoplasm. As a membrane, it is mainly involved in regulating the movements of ions around the cell, and isolating materials that might be harmful or a threat to the cell.

Transport of protons from the cytosol to the vacuole stabilizes cytoplasmic pH, while making the vacuolar interior more acidic creating a proton motive force which the cell can use to transport nutrients into or out of the vacuole. The low pH of the vacuole also allows degradative enzymes to act. Although single large vacuoles are most common, the size and number of vacuoles may vary in different tissues and stages of development. For example, developing cells in the meristems contain small provacuoles and cells of the vascular cambium have many small vacuoles in the winter and one large one in the summer. Aside from storage, the main role of the central vacuole is to maintain turgor pressure against the cell wall. Proteins found in the tonoplast (aquaporins) control the flow of water into and out of the vacuole through active transport, pumping potassium (K+) ions into and out of the vacuolar interior. Due to osmosis, water will diffuse into the vacuole, placing pressure on the cell wall. If water loss leads to a significant decline in turgor pressure, the cell will plasmolyze. Turgor pressure exerted by vacuoles is also required for cellular elongation: as the cell wall is partially degraded by the action of expansins, the less rigid wall is expanded by the pressure coming from within the vacuole. Turgor pressure exerted by the vacuole is also essential in supporting plants in an upright position. Another function of a central vacuole is that it pushes all contents of the cell's cytoplasm against the cellular membrane, and thus keeps the chloroplasts closer to light.[7] Most plants store chemicals in the vacuole that react with chemicals in the cytosol. If the cell is broken, for example by a herbivore, then the two chemicals can react forming toxic chemicals. In garlic, alliin and the enzyme alliinase are normally separated but form allicin if the vacuole is broken. A similar reaction is responsible for the production of syn-propanethial-S-oxide when onions are cut.[citation needed]

The anthocyanin-storing vacuoles of Rhoeo spathacea, a spiderwort, in cells that have plasmolyzed



Vacuoles in fungal cells perform similar functions to those in plants and there can be more than one vacuole per cell. In yeast cells the vacuole is a dynamic structure that can rapidly modify its morphology. They are involved in many processes including the homeostasis of cell pH and the concentration of ions, osmoregulation, storing amino acids and polyphosphate and degradative processes. Toxic ions, such as strontium (Sr2+ ), cobalt(II) (Co2+ ), and lead(II) (Pb2+ ) are transported into the vacuole to isolate them from the rest of the cell.

In animal cells, vacuoles perform mostly subordinate roles, assisting in larger processes of exocytosis and endocytosis. Animal vacuoles are smaller than their plant counterparts but also usually greater in number.[8] There are also animal cells that do not have any vacuoles.[9] Exocytosis is the extrusion process of proteins and lipids from the cell. These materials are absorbed into secretory granules within the Golgi apparatus before being transported to the cell membrane and secreted into the extracellular environment. In this capacity, vacuoles are simply storage vesicles which allow for the containment, transport and disposal of selected proteins and lipids to the extracellular environment of the cell. Endocytosis is the reverse of exocytosis and can occur in a variety of forms. Phagocytosis ("cell eating") is the process by which bacteria, dead tissue, or other bits of material visible under the microscope are engulfed by cells. The material makes contact with the cell membrane, which then invaginates. The invagination is pinched off, leaving the engulfed material in the membrane-enclosed vacuole and the cell membrane intact. Pinocytosis ("cell drinking") is essentially the same process, the difference being that the substances ingested are in solution and not visible under the microscope. Phagocytosis and pinocytosis are both undertaken in association with lysosomes which complete the breakdown of the material which has been engulfed. Salmonella is able to survive and reproduce in the vacuoles of several mammal species after being engulfed.

[1] Venes, Donald (2001). Taber's Cyclopedic Medical Dictionary (Twentieth Edition), (F.A. Davis Company, Philadelphia), p. 2287 ISBN 0-9762548-3-2. [2] Brooker, Robert J, et al. (2007). Biology (First Edition), (McGraw-Hill, New York), p. 79 ISBN 0-07-326807-0. [3] Matile, Phillipe (1993) Chapter 18: Vacuoles, discovery of lysosomal origin in Discoveries in Plant Biology: v. 1 (World Scientific Publishing Co Pte Ltd) [4] Thomas Boller (http:/ / plantbiology. unibas. ch/ people/ boller/ boller. htm). Retrieved on 2011-09-02. [5] http:/ / www. uni-koeln. de/ math-nat-fak/ botanik/ bot1/ AGBecker/ Publikationen/ pdfs/ IRC2007. pdf [6] Alberts, Bruce, Johnson, Alexander, Lewis, Julian, Raff, Martin, Roberts, Keith, and Walter, Peter (2008). Molecular Biology of the Cell (Fifth Edition), (Garland Science, New York), p. 781 ISBN 978-0-8153-4111-6. [7] Lincoln Taiz and Eduardo Zeiger Plant Physiology 3rd Edition SINAUER 2002 p.13 and 14 ISBN 0-87893-856-7 [8] Differences Between Plant and Animal|Cell Procaryotic and Eucaryotic Cell (http:/ / www. icbse. org/ 2010/ 01/ differences-between-plant-and-animal-cell-procaryotic-and-eucaryotic-cell. html). 2011 [9] Plant cells vs. Animal cells (http:/ / www. biology-online. org/ 11/ 1_plant_cells_vs_animal_cells. htm).



Cell biology The animal cell

Components of a typical animal cell: 1. Nucleolus 2. Nucleus 3. Ribosome (little dots) 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus (or "Golgi body") 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytosol (fluid that contains organelles) 12. Lysosome 13. Centrosome 14. Cell membrane

Lysosomes (derived from the Greek words lysis, meaning "to separate", and soma, "body") are the cell's waste disposal system and can digest some compounds. They are used for the digestion of macromolecules from phagocytosis (ingestion of other dying cells or larger extracellular material, like foreign invading microbes), endocytosis (where receptor proteins are recycled from the cell surface), and autophagy (wherein old or unneeded organelles or proteins, or microbes that have invaded the cytoplasm are delivered to the lysosome). Other functions include digesting bacteria (or other forms of waste) that invade a cell and helping repair damage to the plasma membrane by serving as a membrane patch, sealing the wound. In the past, lysosomes were thought to kill cells that are no longer wanted, such as those in the tails of tadpoles or in the web from the fingers of a 3- to 6-month-old fetus.

Christian de Duve, then chairman of the Laboratory of Physiological Chemistry at the Catholic University of Louvain in Belgium, had been studying the mechanism of action of a pancreatic hormone insulin in liver cells. By 1949 he and his team had focussed on the enzyme called glucose 6-phosphatase, which is the first crucial enzyme in sugar metabolism and the target of insulin. They already suspected that this enzyme played a key role in regulating blood sugar levels. However, even after a series of experiments, they failed to purify and isolate the enzyme from the cellular extracts. Therefore they tried a more arduous procedure of cell fractionation, by which cellular components are separated based on their sizes using centrifugation. They succeeded in detecting the enzyme activity from the

Lysosome microsomal fraction. This was the crucial step in the serendipitous discovery. To estimate the enzyme activity, they used that of standardised enzyme acid phosphatase, and found that the activity was quite low (10% of the expected value). One day, the enzyme activity of purified cell fractions which had been refrigerated for five days was measured. Surprisingly the enzyme activity was increased to normal of that of the fresh sample. The result was the same no matter how many times they repeated the estimation. This led to the conclusion that a membrane-like barrier limited the accessibility of the enzyme to its substrate, so that the enzymes were able to diffuse after a few days. They described the membrane-like barrier as a "saclike structure surrounded by a membrane and containing acid phosphatase." It became obvious that an unrelated enzyme from the cell fraction came from a membranous fractions which were definitely cell organelles, and in 1955 De Duve named them "lysosomes" to reflect their digestive properties. That same year, Alex B. Novikoff from the University of Vermont visited de Duves laboratory, and sucessfully obtained the first electron micrographs of the new organelle. Using a staining method for acid phosphatase, de Duve and Novikoff confirmed the location of the hydrolytic enzymes of lysosomes using light and electron microscopic studies. de Duve won the Nobel Prize in Physiology or Medicine in 1974 for this discovery.


Function and structure

Lysosomes are cellular organelles that contain acid hydrolase enzymes that break down waste materials and cellular debris. They can be described as the stomach of the cell. They are found in animal cells, while their existence in yeasts and plants is disputed. Some biologists say the same roles are performed by lytic vacuoles, while others suggest there is strong evidence that lysosomes are indeed found in some plant cells. Lysosomes digest excess or worn-out organelles, food particles, and engulf viruses or bacteria. The membrane around a lysosome allows the digestive enzymes to work at the pH they require. Lysosomes fuse with autophagic vacuoles and dispense their enzymes into the autophagic vacuoles, digesting their contents. They are frequently nicknamed "suicide-bags" or "suicide-sacs" by cell biologists due to their autolysis. A group of genetic inherited disorders called lysosomal storage diseases (LSD) results from the dysfunction of lysosomes. The size of a lysosome varies from 0.11.2 m. At pH 4.8, the interior of the lysosomes is acidic compared to the slightly basic cytosol (pH 7.2). The lysosome maintains this pH differential by pumping protons (H+ ions) from the cytosol across the membrane via proton pumps and chloride ion channels. The lysosomal membrane protects the cytosol, and therefore the rest of the cell, from the degradative enzymes within the lysosome. The cell is additionally protected from any lysosomal acid hydrolases that drain into the cytosol, as these enzymes are pH-sensitive and do not function well or at all in the alkaline environment of the cytosol.This ensures that cytosolic molecules and organelles are not lysed in case there is leakage of the hydrolytic enzymes from the lysosome.

Many components of animal cells are recycled by transferring them inside or embedded in sections of membrane. For instance, in endocytosis, a portion of the cells plasma membrane pinches off to form a vesicle that will eventually fuse with an organelle within the cell. Without active replenishment, the plasma membrane would continuously decrease in size. It is thought that lysosomes participate in this dynamic membrane exchange system and are formed by a gradual maturation process from endosomes. The production of lysosomal proteins suggests one method of lysosome sustainment. Lysosomal protein genes are transcribed in the nucleus. mRNA transcripts exit the nucleus into the cytosol, where they are translated by ribosomes. The nascent peptide chains are translocated into the rough endoplasmic reticulum, where they are modified. Upon exiting the endoplasmic reticulum and entering the Golgi apparatus via vesicular transport, a specific lysosomal tag, mannose 6-phosphate, is added to the peptides. The presence of these tags allow for binding to mannose 6-phosphate receptors in the Golgi apparatus, a phenomenon that is crucial for proper packaging into vesicles destined for the lysosomal system.

Lysosome Upon leaving the Golgi apparatus, the lysosomal enzyme-filled vesicle fuses with a late endosome, a relatively acidic organelle with an approximate pH of 5.5. This acidic environment causes dissociation of the lysosomal enzymes from the mannose 6-phosphate receptors. The enzymes are packed into vesicles for further transport to established lysosomes. The late endosome itself can eventually grow into a mature lysosome, as evidenced by the transport of endosomal membrane components from the lysosomes back to the endosomes.


Weak bases with lipophilic properties accumulate in acidic intracellular compartments like lysosomes. While the plasma and lysosomal membranes are permeable for neutral and uncharged species of weak bases, the charged protonated species of weak bases do not permeate biomembranes and accumulate within lysosomes. The concentration within lysosomes may reach levels 100 to 1000 fold higher than extracellular concentrations. This phenomenon is called "lysosomotropism" or "acid trapping". The amount of accumulation of lysosomotropic compounds may be estimated using a cell based mathematical model. A significant part of the clinically approved drugs are lipophilic weak bases with lysosomotropic properties. This explains a number of pharmacological properties of these drugs, such as high tissue-to-blood concentration gradients or long tissue elimination half-lifes; these properties have been found for drugs such as haloperidol, levomepromazine, and amantadine. However, high tissue concentrations and long elimination half-lives are explained also by lipophilicity and absorption of drugs to fatty tissue structures. Important lysosomal enzymes, such as acid sphingomyelinase, may be inhibited by lysososomally accumulated drugs. Such compounds are termed FIASMAs (functional inhibitor of acid sphingomyelinase) and include for example fluoxetine, sertraline, or amitriptyline.

References External links

This article incorporatespublic domain material from the NCBI document "Science Primer" (http://www.

3D structures of proteins associated with lysosome membrane ( php?localization=Lysosome membrane) Hide and Seek Foundation For Lysosomal Research Team ( Self-Destructive Behavior in Cells May Hold Key to a Longer Life ( science/06cell.html) Mutations in the Lysosomal EnzymeTargeting Pathway and Persistent Stuttering ( content/full/NEJMoa0902630) Animation showing how lysosomes are made, and their function ( 120067/bio01.swf)




The structure of the centrosome

Cell biology The animal cell

Components of a typical animal cell: 1. Nucleolus 2. Nucleus 3. Ribosome (little dots) 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus (or "Golgi body") 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytosol (fluid that contains organelles) 12. Lysosome 13. Centrosome 14. Cell membrane

In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden in 1883. and

Centrosome was described and named in 1888 by Theodor Boveri. The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants use other MTOC structures to organize their microtubules. Although the centrosome has a key role in efficient mitosis in animal cells, it is not essential. Centrosomes are composed of two orthogonally arranged centrioles surrounded by an amorphous mass of protein termed the pericentriolar material (PCM). The PCM contains proteins responsible for microtubule nucleation and anchoring including -tubulin, pericentrin and ninein. In general, each centriole of the centrosome is based on a nine triplet microtubule assembled in a cartwheel structure, and contains centrin, cenexin and tektin.


Roles of the centrosome

Centrosomes are associated with the nuclear membrane during prophase of the cell cycle. In mitosis the nuclear membrane breaks down and the centrosome nucleated microtubules (parts of the cytoskeleton) can interact with the chromosomes to build the mitotic spindle. The mother centriole, the older of the two in the centriole pair, also has a central role in making cilia and flagella. The centrosome is copied only once per cell cycle so that each daughter cell inherits one centrosome, containing two structures called centrioles (see also: centrosome cycle). The centrosome replicates during the S phase of the cell cycle. During the prophase in the Role of the centrosome in cell cycle progression process of cell division called mitosis, the centrosomes migrate to opposite poles of the cell. The mitotic spindle then forms between the two centrosomes. Upon division, each daughter cell receives one centrosome. Aberrant numbers of centrosomes in a cell have been associated with cancer. Doubling of a centrosome is similar to DNA replication in two respects: the semiconservative nature of the process and the action of cdk2 as a regulator of the process. But the processes are essentially different in that centrosome doubling does not occur by template reading and assembly. The mother centriole just aids in the accumulation of materials required for the assembly of the daughter centriole.



Interestingly, centrioles are not required for the progression of mitosis. When the centrioles are irradiated by a laser, mitosis proceeds normally with a morphologically normal spindle. Moreover, development of the fruit fly Drosophila is largely normal when centrioles are absent due to a mutation in a gene required for their duplication. In the absence of the centrioles the microtubules of the spindle are focused by motors allowing the formation of a bipolar spindle. Many cells can Centrosome (shown by arrow) next to nucleus completely undergo interphase without centrioles. Unlike centrioles, centrosomes are required for survival of the organism. Acentrosomal cells lack radial arrays of astral microtubules. They are also defective in spindle positioning and in ability to establish a central localization site in cytokinesis. The function of centrosome in this context is hypothesized to ensure the fidelity of cell division because it greatly increases the efficacy. Some cell types arrest in the following cell cycle when centrosomes are absent. This is not a universal phenomenon. When the nematode C. elegans egg is fertilized the sperm delivers a pair of centrioles. These centrioles will form the centrosomes which will direct the first cell division of the zygote and this will determine its polarity. It's not yet clear whether the role of the centrosome in polarity determination is microtubule dependent or independent.

Centrosome alterations in cancer cells

Theodor Boveri, in 1914, described centrosome aberrations in cancer cells. This initial observation was subsequently extended to many types of human tumors. Centrosome alterations in cancer can be divided in two subgroups, structural or numeric aberrations, yet both can be simultaneously found in a tumor.

Structural aberrations
Usually they appear due to uncontrolled expression of centrosome components, or due to post-translational modifications (such as phosphorylations) which are not adequate for those components. These modifications may produce variations in centrosome size (usually too big, due to an excess of pericentriolar material). On top of this, due to the fact that centrosomal proteins have the tendency to form aggregates, often centrosome-related bodies (CRBs) are observed in ectopic places. Both enlarged centrosomes and CRBs are similar to the centrosomal structures observed in tumors,. Even more, these structures can be induced in culture cells by overexpression of specific centrosomal proteins, such as CNap-1 or Nlp. These structures may look very similar, yet detailed studies reveal that they may present very different properties, depending on their proteic composition. For instance, their capacity to incorporate -TuRC complexes (see also: -tubulin) can be very variable, and so their capacity to nucleate microtubules, therefore affecting in different way the shape, polarity and motility of implicated tumor cells.



Numeric aberrations
The presence of an inadequate number of centrosomes is very often linked to the apparition of genome instability and the loss of tissular differentiation. However, the method to count the centrosome number (each one with 2 centrioles) is often not very precise, because it is frequently assesed using fluorescence microscopy, whose resolution capacity is not the best. Nevertheless, it is clear that the presence of supernumerary (in excess) centrosomes is a common event in human tumors. It has been observed that loss of the tumor-suppressor protein p53 produces supernumerary centrosomes, as well as deregulation of other proteins implicated in tumorigenesis in humans, such as BRCA1 and BRCA2 (for references, see ). It is important to note that supernumerary centrosomes can be generated by very different mechanisms: specific reduplication of the centrosome, failure during cell division (generating an increase in chromosome number), cell fusion (for instance due to infection by specific viruses) or de novo generation of centrosomes. At this point there is not sufficient information to know how frequent are those mechanisms in vivo, but it is possible that the increase in centrosome numbers due a failure during cell division might be more frequent than appreciated, because many "primary" defects in one cell (deregulation of the cell cycle, defective DNA or chromatin metabolism, failure in the spindle checkpoint, etc...) would generate a failure in cell division, an increase in ploidy and an increase in centrosome numbers as a "secondary" effect.

Evolution of the centrosome

The evolutionary history of the centrosome and the centriole has been traced for some of the signature genes, e.g. the centrins. Centrins participate in calcium signaling and are required for centriole duplication. There exist two main subfamilies of centrins, both of which are present in the early-branching eukaryote Giardia intestinalis. Centrins have therefore been present in the common ancestor of eukaryotes. Conversely, they have no recognizable homologs in archea and bacteria and are thus part of the "eukaryotic signature genes." Although there are studies on the evolution of the centrins and centrioles, no studies have been published on the evolution of the pericentriolar material. It is evident that some parts of the centrosome are highly diverged in the model species Drosophila melanogaster and Caenorhabditis elegans. For example, both species have lost one of the centrin subfamilies that are usually associated with centriole duplication. Drosophila melanogaster mutants that lack centrosomes can even develop to morphologically normal adult flies, which then die shortly after birth because their sensory neurons lack cilia. Thus, these flies have evolved functionally redundant machinery, which is independent of the centrosomes.

Centrosome associated nucleotides

Research in 2006 indicated that centrosomes from Surf clam eggs contain RNA sequences. The sequences identified were found in "few to no" other places in the cell, and do not appear in existing genome databases. One identified RNA sequence contains a putative RNA polymerase, leading to the hypothesis of an RNA based genome within the centrosome. However, subsequent research has shown that centrosome do not contain their own DNA-based genomes. While it was confirmed that RNA molecules associate with centrosomes, the sequences have still been found within the nucleus. Furthermore, centrosomes can form de novo after having been removed (e.g. by laser irradiation) from normal cells.




Deoxyribonucleic acid (DNA) is a molecule that encodes the genetic instructions used in the development and functioning of all known living organisms and many viruses. DNA is a nucleic acid; alongside proteins and carbohydrates, nucleic acids compose the three major macromolecules essential for all known forms of life. Most DNA molecules are double-stranded helices, consisting of two long biopolymers made of simpler units called nucleotideseach nucleotide is composed of a nucleobase (guanine, adenine, thymine, and cytosine), recorded using the letters G, A, T, and C, as well as a backbone made of alternating sugars (deoxyribose) and phosphate groups (related to phosphoric acid), with the nucleobases (G, A, T, C) attached to the sugars. DNA is well-suited for biological information storage. The DNA backbone is resistant to cleavage, and both strands of the double-stranded structure store the same biological information. Biological information is replicated as the two strands are separated. The two strands of DNA run in opposite directions to each other and are therefore anti-parallel, one backbone being 3 (three prime) and the other 5 (five prime). This refers to the direction the 3rd and 5th carbon on the sugar molecule is facing. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes biological

The structure of the DNA double helix. The atoms in the structure are colour-coded by element and the detailed structure of two base pairs are shown in the bottom right.

The structure of part of a DNA double helix

DNA information. Under the genetic code, RNA strands are translated to specify the sequence of amino acids within proteins. These RNA strands are initially created using DNA strands as a template in a process called transcription. Within cells, DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed. Scientists use DNA as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials. The obsolete synonym "desoxyribonucleic acid" may occasionally be encountered, for example, in pre-1953 genetics.


DNA is a long polymer made from repeating units called nucleotides.[1] DNA was first identified and isolated by Friedrich Miescher and the double helix structure of DNA was first discovered by James Watson and Francis Crick. The structure of DNA of all species comprises two helical chains each coiled round the same axis, and each with a pitch of 34ngstrms (3.4nanometres) and a radius of 10ngstrms (1.0nanometres). According to another study, when measured in a particular solution, the DNA chain measured 22 to 26ngstrms wide (2.2 to 2.6nanometres), and one nucleotide unit measured 3.3 (0.33nm) long. Although each individual repeating unit is very small, DNA polymers can be very large molecules containing millions of nucleotides. For instance, the largest human chromosome, chromosome number 1, consists of approximately 220 million base pairs and is 85mm long.

Chemical structure of DNA. Hydrogen bonds shown as dotted lines.

In living organisms DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together.[2] These two long strands entwine like vines, in the shape of a double helix. The nucleotide repeats contain both the segment of the backbone of the molecule, which holds the chain together, and a nucleobase, which interacts with the other DNA strand in the helix. A nucleobase linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. A polymer comprising multiple linked

DNA nucleotides (as in DNA) is called a polynucleotide.[3] The backbone of the DNA strand is made from alternating phosphate and sugar residues. The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are called the 5 (five prime) and 3 (three prime) ends, with the 5 end having a terminal phosphate group and the 3 end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA. The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. In the aqueous environment of the cell, the conjugated bonds of nucleotide bases align perpendicular to the axis of the DNA molecule, minimizing their interaction with the solvation shell and therefore, the Gibbs free energy. The four bases found in DNA are adenine (abbreviated A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar/phosphate to form the complete nucleotide, as shown for adenosine monophosphate.


Nucleobase classification
The nucleobases are classified into two types: the purines, A and G, being fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T. A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA a large number of artificial nucleic acid analogues have also been created to study the properties of nucleic acids, or for use in biotechnology.

Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. However in a number of bacteriophages Bacillus subtilis bacteriophages PBS1 and PBS2 and Yersinia bacteriophage piR1-37 thymine has been replaced by uracil.

A section of DNA. The bases lie horizontally between the two [4] spiraling strands. (animated version).

Base J (beta-d-glucopyranosyloxymethyluracil), a modified form of uracil, is also found in a number of organisms: the flagellates Diplonema and Euglena, and all the kinetoplastid genera Biosynthesis of J occurs in two steps: in the first step a specific thymidine in DNA is converted into hydroxymethyldeoxyuridine; in the second HOMedU is glycosylated to form J. Proteins that bind specifically to this base have been identified. These proteins appear to be distant relatives of the Tet1 oncogene that is involved in the pathogenesis of acute myeloid leukemia. J appears to act as a termination signal for RNA polymerase II.



Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. One groove, the major groove, is 22 wide and the other, the minor groove, is 12 wide. The narrowness of the minor groove means that the edges of the bases are Major and minor grooves of DNA. Minor groove more accessible in the major groove. As a result, proteins like is a binding site for the dye Hoechst 33258. transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

Base pairing
In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature. As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.

Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines. The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). DNA with high GC-content is more stable than DNA with low GC-content. As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double stranded structure (dsDNA) is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart a process known as melting to form two single-stranded DNA molecules (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

DNA The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart. In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules (ssDNA) have no single common shape, but some conformations are more stable than others.


Sense and antisense

A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein.[5] The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing. A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.

Alternate DNA structures

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, as well as the presence of polyamines in solution.

From left to right, the structures of A, B and Z DNA

DNA The first published reports of A-DNA X-ray diffraction patternsand also B-DNAused analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. An alternate analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction/scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix. Although the "B-DNA form" is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations[6] that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.[7] Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partially dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.


Alternate DNA chemistry

For a number of years exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1, was announced, though the research was disputed, and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.

Quadruplex structures
At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3 ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence. These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure. In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded
DNA quadruplex formed by telomere repeats. The looped conformation of the DNA backbone [8] is very different from the typical DNA helix.

DNA DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.


Single branch

Multiple branches

Branched DNA can form networks containing multiple branches.

Branched DNA
In DNA fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible. Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

Chemical modifications and altered DNA packaging




Structure of cytosine with and without the 5-methyl group. Deamination converts 5-methylcytosine into thymine.

Base modifications and DNA packaging

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.[9] For one example, cytosine methylation, produces 5-methylcytosine, which is important for X-chromosome inactivation. The average level of methylation varies between organisms the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations. Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain, and the glycosylation of uracil to produce the "J-base" in kinetoplastids.



DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. A typical human cell contains about 150,000 bases that have suffered oxidative damage. Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions and deletions from the DNA sequence, as well as chromosomal translocations. These mutations can cause cancer. Because of inherent limitations in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer. A covalent adduct between a metabolically DNA damages that are naturally occurring, due to normal cellular activated form of benzo[a]pyrene, the major [10] processes that produce reactive oxygen species, the hydrolytic mutagen in tobacco smoke, and DNA activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.[11] Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen. Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication. Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.

Biological functions
DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here we focus on the interactions between DNA and other molecules that mediate the function of the genome.



Genes and genomes

Genomic DNA is tightly and orderly packed in the process called DNA condensation to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, as well as small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, as well as regulatory sequences such as promoters and enhancers, which control the transcription of the open reading frame. In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences. The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species represent a long-standing puzzle known as the "C-value enigma". However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression. Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes, but are important for the function and stability of chromosomes. An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.

Transcription and translation

T7 RNA polymerase (blue) producing a mRNA [12] (green) from a DNA template (orange).

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons ( combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA and TAG codons.



Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are DNA replication. The double helix is unwound by a helicase and topoisomerase. Next, separated and then each strand's one DNA polymerase produces the leading strand copy. Another DNA polymerase binds complementary DNA sequence is to the lagging strand. This enzyme makes discontinuous segments (called Okazaki fragments) before DNA ligase joins them together. recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing, and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5 to 3 direction, different mechanisms are used to copy the antiparallel strands of the double helix. In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

Interactions with proteins

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

DNA-binding proteins

Interaction of DNA (shown in orange) with histones (shown in blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA. Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. Other non-specific DNA-binding

DNA proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes. A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases. In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase. As these DNA targets can occur throughout an organism's genome, changes in The lambda repressor the activity of one type of transcription factor can affect thousands of genes. helix-turn-helix transcription factor Consequently, these proteins are often the targets of the signal transduction [13] bound to its DNA target processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.


DNA-modifying enzymes
Nucleases and ligases Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which The restriction enzyme EcoRV (green) in a [14] cut DNA at specific sequences. For instance, the EcoRV enzyme complex with its substrate DNA shown to the left recognizes the 6-base sequence 5-GATATC-3 and makes a cut at the vertical line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system. In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting. Enzymes called DNA ligases can rejoin cut or broken DNA strands. Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.

DNA Topoisomerases and helicases Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break. Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix. Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription. Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly ATP, to break hydrogen bonds between bases and unwind the DNA double helix into single strands. These enzymes are essential for most processes where enzymes need to access the DNA bases. Polymerases Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products are created based on existing polynucleotide chainswhich are called templates. These enzymes function by repeatedly adding a nucleotide to the 3 hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5 to 3 direction. In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use. In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. In order to preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3 to 5 exonuclease activity is activated and the incorrect base removed. In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases. RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres. Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.




Genetic recombination

Structure of the Holliday junction intermediate in genetic recombination. The four separate DNA strands are coloured red, blue, green and yellow.[15] A DNA helix usually does not interact with other segments of DNA, and in human cells the different chromosomes even occupy separate areas in the nucleus called "chromosome territories". This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is during chromosomal crossover when they recombine. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin. Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins. Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks. The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51. The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA. A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.
Recombination involves the breakage and rejoining of two chromosomes (M and F) to produce two re-arranged chromosomes (C1 and C2).



DNA contains the genetic information that allows all modern living things to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material. RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes. This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes. However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible. This is because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution. Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old, but these claims are controversial. On 8 August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting building blocks of DNA (adenine, guanine and related organic molecules) may have been formed extraterrestrially in outer space.

Uses in technology
Genetic engineering
Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector. The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research, or be grown in agriculture.

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is formally termed DNA profiling, but may also be called "genetic fingerprinting". In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA. However, identification can be complicated if the scene is contaminated with DNA from several people. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys, and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.[16] The development of forensic science, and the ability to now obtain genetic matching on minute samples of blood, skin, saliva or hair has led to a re-examination of a number of cases. Evidence can now be uncovered that was not scientifically possible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where previous trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defence to DNA matches obtained forensically is to claim that cross-contamination of evidence has taken place. This has resulted in meticulous strict handling procedures with new cases of serious crime. DNA profiling is also used to identify victims of mass casualty incidents. As well as positively identifying bodies or body parts in serious accidents, DNA profiling is being successfully used to identify individual victims in mass war graves matching to family members.



Bioinformatics involves the manipulation, searching, and data mining of biological data, and this includes DNA sequence data. The development of techniques to store and search DNA sequences have led to widely applied advances in computer science, especially string searching algorithms, machine learning and database theory. String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides.[17] The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function. Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally. Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

DNA nanotechnology
DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties. DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based as well as using the "DNA origami" method) as well as three-dimensional The DNA structure at left (schematic shown) will self-assemble into the structure structures in the shapes of polyhedra. visualized by atomic force microscopy at right. DNA nanotechnology is the field that seeks to design nanoscale structures using the molecular recognition properties of DNA Nanomechanical devices and [18] molecules. Image from Strong, 2004 . algorithmic self-assembly have also been demonstrated, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.

History and anthropology

Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny. This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology; For example, DNA evidence is being used to try to identify the Ten Lost Tribes of Israel.[19][20] DNA has also been used to look at modern family relationships, such as establishing family relationships between the descendants of Sally Hemings and Thomas Jefferson. This usage is closely related to the use of DNA in criminal

DNA investigations detailed above. Indeed, some criminal investigations have been solved when DNA from crime scenes has matched relatives of the guilty individual.[21]


Information storage
In a paper published in Nature in January, 2013, scientists from the European Bioinformatics Institute and Agilent Technologies proposed a mechanism to use DNA's ability to code information as a means of digital data storage. The group was able to encode 739 kilobytes of data into DNA code, synthesize the actual DNA, then sequence the DNA and decode the information back to its original form, with a reported 100% accuracy. The encoded information consisted of text files and audio files. A prior experiment was published in August 2012. It was conducted by researchers at Harvard University, where the text of a 54,000-word book was encoded in DNA.

History of DNA research

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein". In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases. In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit. Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However, Levene thought the chain was short and the bases repeated in a fixed order. In 1937 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.

James Watson and Francis Crick (right), co-originators of the double-helix model, with Maclyn McCarty (left).

In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template". In 1928, Frederick Griffith in his experiment discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. This system provided the first clear suggestion that DNA carries genetic informationthe AveryMacLeodMcCarty experimentwhen Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943. DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the HersheyChase experiment showed that DNA is the genetic material of the T2 phage. In 1953, James Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. Their double-helix, molecular model of DNA was then based on a single X-ray diffraction image (labeled as "Photo 51")[22] taken by Rosalind Franklin and Raymond Gosling in May 1952, as well as the information that the DNA bases are paired also obtained through private communications from Erwin Chargaff in the previous years. Chargaff's rules played a very important role in establishing double-helix configurations for B-DNA as well as A-DNA. Experimental evidence supporting the Watson and Crick model was published in a series of five articles in the same issue of Nature.[23] Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partially supported the Watson and Crick model; this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the previous two pages of Nature. In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine.[24] Nobel

DNA Prizes were awarded only to living recipients at the time. A debate continues about who should receive credit for the discovery. In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".[25] Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the MeselsonStahl experiment. Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code.[26] These findings represent the birth of molecular biology.


[1] pp. 1415. [2] Berg J., Tymoczko J. and Stryer L. (2002) Biochemistry. W. H. Freeman and Company ISBN 0-7167-4955-6 [3] Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents (http:/ / www. chem. qmul. ac. uk/ iupac/ misc/ naabb. html) IUPAC-IUB Commission on Biochemical Nomenclature (CBN). Retrieved 3 January 2006. [4] Created from PDB 1D65 (http:/ / www. rcsb. org/ pdb/ cgi/ explore. cgi?pdbId=1D65) [5] Designation of the two strands of DNA (http:/ / www. chem. qmul. ac. uk/ iubmb/ newsletter/ misc/ DNA. html) JCBN/NC-IUB Newsletter 1989. Retrieved 7 May 2008 [6] http:/ / cogprints. org/ 3822/ [7] Hosemann R., Bagchi R.N., Direct analysis of diffraction by matter, North-Holland Publs., Amsterdam New York, 1962. [8] Created from NDB UD0017 (http:/ / ndbserver. rutgers. edu/ atlas/ xray/ structures/ U/ ud0017/ ud0017. html) [9] Hu Q, Rosenfeld MG. (2012) Epigenetic regulation of human embryonic stem cells. Front Genet. 3:238. doi: 10.3389/fgene.2012.00238. PMID 23133442 [10] Created from PDB 1JDG (http:/ / www. rcsb. org/ pdb/ cgi/ explore. cgi?pdbId=1JDG) [11] Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). Cancer and aging as consequences of un-repaired DNA damage. In: New Research on DNA Damages (Editors: Honoka Kimura and Aoi Suzuki) Nova Science Publishers, Inc., New York, Chapter 1, pp. 1-47. open access, but read only https:/ / www. novapublishers. com/ catalog/ product_info. php?products_id=43247 ISBN 1604565810 ISBN 978-1604565812 [12] Created from PDB 1MSW (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=1MSW) [13] Created from PDB 1LMB (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=1LMB) [14] Created from PDB 1RVA (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=1RVA) [15] Created from PDB 1M6G (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=1M6G) [16] Colin Pitchfork first murder conviction on DNA evidence also clears the prime suspect (http:/ / web. archive. org/ web/ 20061214004903/ http:/ / www. forensic. gov. uk/ forensic_t/ inside/ news/ list_casefiles. php?case=1) Forensic Science Service Accessed 23 December 2006 [17] Gusfield, Dan. Algorithms on Strings, Trees, and Sequences: Computer Science and Computational Biology. Cambridge University Press, 15 January 1997. ISBN 978-0-521-58519-4. [18] http:/ / dx. doi. org/ 10. 1371/ journal. pbio. 0020073 [19] Lost Tribes of Israel, NOVA, PBS airdate: 22 February 2000. Transcript available from (http:/ / www. pbs. org/ wgbh/ nova/ transcripts/ 2706israel. html). Retrieved 4 March 2006. [20] Kleiman, Yaakov. "The Cohanim/DNA Connection: The fascinating story of how DNA studies confirm an ancient biblical tradition". (http:/ / www. aish. com/ societywork/ sciencenature/ the_cohanim_-_dna_connection. asp) (13 January 2000). Retrieved 4 March 2006. [21] Bhattacharya, Shaoni. "Killer convicted thanks to relative's DNA". (http:/ / www. newscientist. com/ article. ns?id=dn4908) (20 April 2004). Retrieved 22 December 06. [22] The B-DNA X-ray pattern on the right of this linked image (http:/ / osulibrary. oregonstate. edu/ specialcollections/ coll/ pauling/ dna/ pictures/ sci9. 001. 5. html) was obtained by Rosalind Franklin and Raymond Gosling in May 1952 at high hydration levels of DNA and it has been labeled as "Photo 51" [23] Nature Archives Double Helix of DNA: 50 Years (http:/ / www. nature. com/ nature/ dna50/ archive. html) [24] The Nobel Prize in Physiology or Medicine 1962 (http:/ / nobelprize. org/ nobel_prizes/ medicine/ laureates/ 1962/ ) Nobelprize .org Accessed 22 December 06 [25] Crick, F.H.C. On degenerate templates and the adaptor hypothesis (PDF). (http:/ / genome. wellcome. ac. uk/ assets/ wtx030893. pdf) (Lecture, 1955). Retrieved 22 December 2006. [26] The Nobel Prize in Physiology or Medicine 1968 (http:/ / nobelprize. org/ nobel_prizes/ medicine/ laureates/ 1968/ ) Accessed 22 December 06



Further reading
Berry, Andrew; Watson, James. (2003). DNA: the secret of life. New York: Alfred A. Knopf. ISBN0-375-41546-7. Calladine, Chris R.; Drew, Horace R.; Luisi, Ben F. and Travers, Andrew A. (2003). Understanding DNA: the molecule & how it works. Amsterdam: Elsevier Academic Press. ISBN0-12-155089-3. Dennis, Carina; Julie Clayton (2003). 50 years of DNA. Basingstoke: Palgrave Macmillan. ISBN1-4039-1479-6. Judson, Horace F. 1979. The Eighth Day of Creation: Makers of the Revolution in Biology. Touchstone Books, ISBN 0-671-22540-5. 2nd edition: Cold Spring Harbor Laboratory Press, 1996 paperback: ISBN 0-87969-478-5. Olby, Robert C. (1994). The path to the double helix: the discovery of DNA. New York: Dover Publications. ISBN0-486-68117-3., first published in October 1974 by MacMillan, with foreword by Francis Crick;the definitive DNA textbook,revised in 1994 with a 9 page postscript Micklas, David. 2003. DNA Science: A First Course. Cold Spring Harbor Press: ISBN 978-0-87969-636-8 Ridley, Matt (2006). Francis Crick: discoverer of the genetic code. Ashland, OH: Eminent Lives, Atlas Books. ISBN0-06-082333-X. Olby, Robert C. (2009). Francis Crick: A Biography. Plainview, N.Y: Cold Spring Harbor Laboratory Press. ISBN0-87969-798-9. Rosenfeld, Israel. 2010. DNA: A Graphic Guide to the Molecule that Shook the World. Columbia University Press: ISBN 978-0-231-14271-7 Schultz, Mark and Zander Cannon. 2009. The Stuff of Life: A Graphic Guide to Genetics and DNA. Hill and Wang: ISBN 0-8090-8947-5 Stent, Gunther Siegmund; Watson, James. (1980). The double helix: a personal account of the discovery of the structure of DNA. New York: Norton. ISBN0-393-95075-1. Watson, James. 2004. DNA: The Secret of Life. Random House: ISBN 978-0-09-945184-6 Wilkins, Maurice (2003). The third man of the double helix the autobiography of Maurice Wilkins. Cambridge, Eng: University Press. ISBN0-19-860665-6.

External links
Library resources
About DNA

Online books ( Resources in your library ( Resources in other libraries (

DNA ( Nucleic_Acids/DNA//) at the Open Directory Project DNA binding site prediction on protein ( DNA the Double Helix Game ( From the official Nobel Prize web site DNA under electron microscope ( Dolan DNA Learning Center ( Double Helix: 50 years of DNA (, Nature Proteopedia DNA ( Proteopedia Forms_of_DNA ( ENCODE threads explorer ( ENCODE Home page. Nature (journal) Double Helix 19532003 ( National Centre for Biotechnology Education

DNA Genetic Education Modules for Teachers ( from the Beginning Study Guide PDB Molecule of the Month pdb23_1 ( molecule_of_the_month/pdb23_1.html) Rosalind Franklin's contributions to the study of DNA ( U.S. National DNA Day ( videos and participate in real-time chat with top scientists Clue to chemistry of heredity found ( The New York Times June 1953. First American newspaper coverage of the discovery of the DNA structure Olby R (2003). "Quiet debut for the double helix". Nature 421 (6921): 4025. Bibcode: 2003Natur.421..402O ( doi: 10.1038/nature01397 ( 1038/nature01397). PMID 12540907 ( DNA from the Beginning ( Another DNA Learning Center site on DNA, genes, and heredity from Mendel to the human genome project. The Register of Francis Crick Personal Papers 1938 2007 ( mss0660a.html#abstract) at Mandeville Special Collections Library, University of California, San Diego Seven-page, handwritten letter that Crick sent to his 12-year-old son Michael in 1953 describing the structure of DNA. (!/file/Crick letter to Michael.pdf) See Cricks medal goes under the hammer (, Nature, 5 April 2013.


Part of a series on

Key components

Chromosome DNA RNA Genome Heredity Mutation Nucleotide Variation Glossary Index Outline History and topics

Introduction History Evolution (molecular) Population genetics Mendelian inheritance Quantitative genetics Molecular genetics



DNA sequencing Genetic engineering Genomics ( template) Medical genetics Branches of genetics Biology portal

In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of viruses, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA.[1]

Origin of term
The term was created in 1920 by Hans Winkler, professor of botany at the University of Hamburg, Germany. The Oxford English Dictionary suggests the name to be a blend of the words gene and chromosome. A few related -ome words already existedsuch as biome, rhizome and, more recently, connectomeforming a vocabulary into which genome fits systematically.

An image of the 46 chromosomes making up the diploid genome of a human male. (The mitochondrial chromosome is not shown.)

Some organisms have multiple copies of chromosomes: diploid, triploid, tetraploid and so on. In classical genetics, in a sexually reproducing organism (typically eukarya) the gamete has half the number of chromosomes of the somatic cell and the genome is a full set of chromosomes in a gamete. In haploid organisms, including cells of bacteria, archaea, and in organelles including mitochondria and chloroplasts, or viruses, that similarly contain genes, the single or set of circular and/or linear chains of DNA (or RNA for some viruses), likewise constitute the genome. The term genome can be applied specifically to mean what is stored on a complete set of nuclearDNA (i.e.,the "nuclear genome") but can also be applied to what is stored within organelles that contain their own DNA, as with the "mitochondrial genome" or the "chloroplast genome". Additionally, the genome can comprise non-chromosomal genetic elements such as viruses, plasmids, and transposable elements. When people say that the genome of a sexually reproducing species has been "sequenced", typically they are referring to a determination of the sequences of one set of autosomes and one of each type of sex chromosome, which together represent both of the possible sexes. Even in species that exist in only one sex, what is described as a "genome sequence" may be a composite read from the chromosomes of various individuals. Colloquially, the phrase "genetic makeup" is sometimes used to signify the genome of a particular individual or organism. The study of the global properties of genomes of related organisms is usually referred to as genomics, which distinguishes it from genetics which generally studies the properties of single genes or groups of genes. Both the number of base pairs and the number of genes vary widely from one species to another, and there is only a rough correlation between the two (an observation known as the C-value paradox). At present, the highest known number of genes is around 60,000, for the protozoan causing trichomoniasis (see List of sequenced eukaryotic genomes), almost three times as many as in the human genome.

Genome An analogy to the human genome stored on DNA is that of instructions stored in a book: The book (genome) would contain 23chapters (chromosomes); Each chapter contains 48 to 250million letters (A,C,G,T) without spaces; Hence, the book contains over 3.2billion letters total; The book fits into a cell nucleus the size of a pinpoint; At least one copy of the book (all 23chapters) is contained in most cells of our body. The only exception in humans is found in mature red blood cells which become enucleated during development and therefore lack a genome.


Sequencing and mapping

In 1976, Walter Fiers at the University of Ghent (Belgium) was the first to establish the complete nucleotide sequence of a viral RNA-genome (bacteriophage MS2). The next year, Phage -X174, with only 5386 base pairs, became the first DNA-genome project to be completed, by Fred Sanger. The first complete genome sequences for representatives from all 3 domains of life were released within a short period during the mid-1990s. The first bacterial genome to be sequenced was that of Haemophilus influenzae, completed by a team at The Institute for Genomic Research in 1995. A few months later, the first eukaryotic genome was completed, with the 16 chromosomes of budding yeast Saccharomyces cerevisiae being released as the result of a European-led effort begun in the mid-1980s. Shortly afterward, in 1996, the first genome sequence for an archaeon, Methanococcus jannaschii, was completed, again by The Institute for Genomic Research. The development of new technologies has made it dramatically easier and cheaper to do sequencing, and the number of complete genome sequences is growing rapidly. The US National Institutes of Health maintains one of several comprehensive databases of genomic information. Among the thousands of completed genome sequencing projects include those for mouse, rice, the plant Arabidopsis thaliana, the puffer fish, and bacteria like E. coli. New sequencing technologies, such as massive parallel sequencing have also opened up the prospect of personal genome sequencing as a diagnostic tool, as pioneered by Manteia Predictive Medicine. A major step toward that goal was the completion in 2007 of the full genome of James D. Watson, one of the co-discoverers of the structure of DNA. Whereas a genome sequence lists the order of every DNA base in a genome, a genome map identifies the landmarks. A genome map is less detailed than a genome sequence and aids in navigating around the genome. The Human Genome Project was organized to map and to sequence the human genome. A fundamental step in the project was the release of a detailed genomic map by Jean Weissenbach and his team at the Genoscope in Paris.

Genome compositions
Genome composition is used to describe the make up of contents of a haploid genome, which should include genome size, proportions of non-repetitive DNA and repetitive DNA in details. By comparing the genome compositions between genomes, scientists can better understand the evolutionary history of a given genome. When talking about genome composition, one should distinguish between prokaryotes and eukaryotes as the big differences on contents structure they have. In prokaryotes, most of the genome (85-90%) is non-repetitive DNA, which means coding DNA mainly forms it, while non-coding regions only take a small part. On the contrary, eukaryotes have the feature of exon-intron organization of protein coding genes; the variation of repetitive DNA content in eukaryotes is also extremely high. When refer to mammalians and plants, the major part of genome is composed by repetitive DNA. Most biological entities that are more complex than a virus sometimes or always carry additional genetic material besides that which resides in their chromosomes. In some contexts, such as sequencing the genome of a pathogenic microbe, "genome" is meant to include information stored on this auxiliary material, which is carried in plasmids. In

Genome such circumstances then, "genome" describes all of the genes and information on non-coding DNA that have the potential to be present. In eukaryotes such as plants, protozoa and animals, however, "genome" carries the typical connotation of only information on chromosomal DNA. So although these organisms contain chloroplasts and/or mitochondria that have their own DNA, the genetic information contained by DNA within these organelles is not considered part of the genome. In fact, mitochondria are sometimes said to have their own genome often referred to as the "mitochondrial genome". The DNA found within the chloroplast may be referred to as the "plastome".


Genome size
Genome size is the total number of DNA base pairs in one copy of a haploid genome. The genome size is positively correlated with the morphological complexity among prokaryotes and lower eukaryotes; however, after mollusks and all the other higher eukaryotes above, this correlation is no longer effective. This phenomenon also indicates the mighty influence coming from repetitive DNA act on the genomes. Since genomes are very complex, one research strategy is to reduce the number of genes in a genome to the bare minimum and still have the organism in question survive. There is experimental work being done on minimal genomes for single cell organisms as well as minimal genomes for multi-cellular organisms (see Developmental biology). The work is both in vivo and in silico.
Organism type Virus Virus Virus Virus Virus Virus Virus Virus Bacterium Bacterium Bacterium Bacterium Bacterium Bacterium Organism Genome size (base pairs) 1,759 1.8kb 3,569 3.5kb 5,224 5.2kb 5,386 5.4kb 9,749 9.7kb 48,502 48kb 1,259,197 1.3Mb Often used as a vector for the cloning of recombinant DNA. Until 2013 the largest known viral genome. First sequenced DNA-genome

Log-log plot of the total number of annotated proteins in genomes submitted to GenBank as a function of genome size.


Porcine circovirus type 1 Bacteriophage MS2 SV40 Phage -X174 HIV Phage Megavirus Pandoravirus salinus Haemophilus influenzae Carsonella ruddii Buchnera aphidicola Wigglesworthia glossinidia Escherichia coli Solibacter usitatus (strain Ellin 6076) Polychaos dubium ("Amoeba" dubia) Arabidopsis thaliana Genlisea margaretae

Smallest viruses replicating autonomously in eukaryotic cells. First sequenced RNA-genome

2,470,000 2.47Mb Largest known viral genome. 1,830,000 1.8Mb 159,662 160kb 600,000 600kb 700,000 700Kb 4,600,000 4.6Mb 9,970,000 10Mb First genome of a living organism sequenced, July 1995 Smallest non-viral genome.


670,000,000,000 670Gb

Largest known genome. (Disputed


Plant Plant

157,000,000 157Mb 63,400,000 63Mb

First plant genome sequenced, December 2000. Smallest recorded flowering plant genome, 2006.


Fritillaria assyrica Populus trichocarpa 130,000,000,000 130Gb 480,000,000 480Mb First tree genome sequenced, September 2006 Largest plant genome known

Plant Plant Plant

Paris japonica (Japanese-native, 150,000,000,000 150Gb pale-petal) Physcomitrella patens Saccharomyces cerevisiae Aspergillus nidulans Caenorhabditis elegans Pratylenchus coffeae Drosophila melanogaster (fruit fly) Bombyx mori (silk moth) Apis mellifera (honey bee) Solenopsis invicta (fire ant) Tetraodon nigroviridis (type of puffer fish) Mus musculus Homo sapiens 480,000,000 480Mb

Moss Yeast Fungus Nematode Nematode Insect

First genome of a bryophyte sequenced, January 2008.

12,100,000 12.1Mb First eukaryotic genome sequenced, 1996 30,000,000 30Mb 100,300,000 100Mb 20,000,000 20Mb 130,000,000 130Mb First multicellular animal genome sequenced, December 1998 Smallest animal genome known

Insect Insect Insect Fish

432,000,000 432Mb 236,000,000 236Mb 480,000,000 480Mb 385,000,000 390Mb

14,623 predicted genes

Smallest vertebrate genome known estimated to be 340 Mb - 385 Mb.

Mammal Mammal

2,700,000,000 2.7Gb 3,200,000,000 3.2Gb Homo sapiens estimated genome size 3.2 billion bp sequencing and analysis of the human genome Largest vertebrate genome known [3] Initial


Protopterus aethiopicus (marbled lungfish)

130,000,000,000 130Gb

Proportion of non-repetitive DNA

The proportion of non-repetitive DNA is calculated by using length of non-repetitive DNA divided by genome size. Protein-coding genes and RNA-coding genes are generally non-repetitive DNA. Bigger genome does not mean more genes, and the proportion of non-repetitive DNA decreases along with the increase of genome size in higher eukaryotes. It had been found that the proportion of non-repetitive DNA can vary a lot between species. Some E. coli as prokaryotes only have non-repetitive DNA, lower eukaryotes such as C. elegans and fruit fly, still possess more non-repetitive DNA than repetitive DNA. Higher eukaryotes tend to have more repetitive DNA than non-repetitive one. In some plants and amphibians, the proportion of non-repetitive DNA is no more than 20%, becoming a minority component.

Proportion of repetitive DNA

The proportion of repetitive DNA is calculated by using length of repetitive DNA divide by genome size. There are two categories of repetitive DNA in genome: tandem repeats and interspersed repeats. Tandem repeats Tandem repeats are usually caused by slippage during replication, unequal crossing-over and gene conversion, satellite DNA and microsatellites are forms of tandem repeats in the genome. Although tandem repeats count for a significant proportion in genome, the largest proportion in mammalian is the other type, interspersed repeats.

Genome Interspersed repeats Interspersed repeats mainly come from transposable elements (TEs), but they also include some protein coding gene families and pseudogenes. Transposable elements are able to integrate into the genome at another site within the cell. It is believed that TEs are an important driving force on genome evolution of higher eukaryotes. TEs can be classified into two categories, Class 1 (retrotransposons) and Class 2 (DNA transposons). Retrotransposons Retrotransposons can be transcribed into RNA, which are then duplicated at another site into the genome. Retrotransposons can be divided into Long terminal repeats (LTRs) and Non-Long Terminal Repeats (Non-LTR). Long Terminal Repeats (LTRs) similar to retroviruses, which have both gag and pol genes to make cDNA from RNA and proteins to insert into genome, but LTRs can only act within the cell as they lack the env gene in retroviruses. It has been reported that LTRs consist of the largest fraction in most plant genome and might account for the huge variation in genome size. Non-Long Terminal Repeats (Non-LTRs) can be divided into long interspersed elements (LINEs), short interspersed elements (SINEs) and Penelope-like elements. In Dictyostelium discoideum, there is another DIRS-like elements belong to Non-LTRs. Non-LTRs are widely spread in eukaryotic genomes. Long interspersed elements (LINEs) are able to encode two Open Reading Frames (ORFs) to generate transcriptase and endonuclease, which are essential in retrotransposition. The human genome has around 500,000 LINEs, taking around 17% of the genome. Short interspersed elements (SINEs) are usually less than 500 base pairs and need to co-opt with the LINEs machinery to function as nonautonomous retrotransposons. The Alu element is the most common SINEs found in primates, it has a length of about 350 base pairs and takes about 11% of the human genome with around 1,500,000 copies. DNA transposons DNA transposons generally move by "cut and paste" in the genome, but duplication has also been observed. Class 2 TEs do not use RNA as intermediate and are popular in bacteria, in metazoan it has also been found.


Genome evolution
Genomes are more than the sum of an organism's genes and have traits that may be measured and studied without reference to the details of any particular genes and their products. Researchers compare traits such as chromosome number (karyotype), genome size, gene order, codon usage bias, and GC-content to determine what mechanisms could have produced the great variety of genomes that exist today (for recent overviews, see Brown 2002; Saccone and Pesole 2003; Benfey and Protopapas 2004; Gibson and Muse 2004; Reese 2004; Gregory 2005). Duplications play a major role in shaping the genome. Duplication may range from extension of short tandem repeats, to duplication of a cluster of genes, and all the way to duplication of entire chromosomes or even entire genomes. Such duplication's are probably fundamental to the creation of genetic novelty. Horizontal gene transfer is invoked to explain how there is often extreme similarity between small portions of the genomes of two organisms that are otherwise very distantly related. Horizontal gene transfer seems to be common among many microbes. Also, eukaryotic cells seem to have experienced a transfer of some genetic material from their chloroplast and mitochondrial genomes to their nuclear chromosomes.



[1] Ridley, M. (2006). Genome. New York, NY: Harper Perennial. ISBN 0-06-019497-9 [2] ScienceShot: Biggest Genome Ever (http:/ / news. sciencemag. org/ sciencenow/ 2010/ 10/ scienceshot-biggest-genome-ever. html), comments: "The measurement for Amoeba dubia and other protozoa which have been reported to have very large genomes were made in the 1960s using a rough biochemical approach which is now considered to be an unreliable method for accurate genome size determinations." [3] http:/ / www. ornl. gov/ sci/ techresources/ Human_Genome/ faq/ compgen. shtml#genomesize

Further reading
Benfey, P.; Protopapas, A.D. (2004). Essentials of Genomics. Prentice Hall. Brown, Terence A. (2002). Genomes 2. Oxford: Bios Scientific Publishers. ISBN978-1-85996-029-5. Gibson, Greg; Muse, Spencer V. (2004). A Primer of Genome Science (Second ed.). Sunderland, Mass: Sinauer Assoc. ISBN0-87893-234-8. Gregory, T. Ryan (ed) (2005). The Evolution of the Genome. Elsevier. ISBN0-12-301463-8. Reece, Richard J. (2004). Analysis of Genes and Genomes. Chichester: John Wiley & Sons. ISBN0-470-84379-9. Saccone, Cecilia; Pesole, Graziano (2003). Handbook of Comparative Genomics. Chichester: John Wiley & Sons. ISBN0-471-39128-X. Werner, E. (2003). "In silico multicellular systems biology and minimal genomes". Drug Discov Today 8 (24): 11211127. doi: 10.1016/S1359-6446(03)02918-0 ( PMID 14678738 (

External links
UCSC Genome Browser ( - view the genome and annotations for more than 80 organisms. ( Build a DNA Molecule ( Some comparative genome sizes ( shtml) DNA Interactive: The History of DNA Science ( DNA From The Beginning ( All About The Human Genome Project ( Animal genome size database ( Plant genome size database ( GOLD:Genomes OnLine Database ( The Genome News Network ( NCBI Entrez Genome Project database ( NCBI Genome Primer ( GeneCards ( integrated database of human genes BBC News - Final genome 'chapter' published ( IMG ( (The Integrated Microbial Genomes system)for genome analysis by the DOE-JGI GeKnome Technologies Next-Gen Sequencing Data Analysis ( sequencing data analysis for Illumina and 454 Service from GeKnome Technologies.

Article Sources and Contributors


Article Sources and Contributors

Cell (biology) Source: Contributors: .:Ajvol:., 041744, 168..., 1pezguy, 1tinyboo, 2004-12-29T22:45Z,, 2D, 2help, 2over0, 83d40m, A3RO, A8UDI, A:f6, AOB, Abbypettis, Abdullais4u, Acalamari, Acather96, Accurizer, Ace of Spades, Acer al2017, Acroterion, Adam.J.W.C., Adam78, AdamRetchless, Adamstevenson, Adapter, Adenosine, AdjustShift, Aeonx, Afctenfour, Ahoerstemeier, Ahora, Ajh16, Ajraddatz, Akanemoto, Akradecki, Alan Liefting, Alansohn, Ale jrb, AlexiusHoratius, Alisonthegreat, Alvarogonzalezsotillo, Alxeedo, Amren, AnakngAraw, Anclation, Andonic, Andre Engels, Andrea105, Andres, Andrew4010, Andy120290, Andycjp, Animum, Anna Lincoln, Anonymous Dissident, Anphanax, Antandrus, Anthere, Arcadian, ArglebargleIV, Arjun01, Art LaPella, Arti Sahajpal, Ascidian, Aua, AuburnPilot, Average Earthman, Avicennasis, Avono, Avs5221, AxelBoldt, BMBTHC, Backslash Forwardslash, Bart133, Bbasen, Bcorr, Bearly541, BenBaker, Bencherlite, Bensaccount, Bernstein0275, Betacommand, Bhartta, Biji123, Bility, Bjarki S, Blackdeath15, Blanchardb, Blogeswar, Blue520, Bob rulz, Bobo192, Bodiejnr, Bogey97, Boing! said Zebedee, Bongwarrior, Bookgeek10, Bookwormlady1100, BorgHunter, BorgQueen, Bourgeb, BradBeattie, Bradeos Graphon, Bradht2710, Brainmuncher, Brazucs, Brian Brondel, Brianga, Brion VIBBER, BrotherE, BruceBlaus, Bruceplayzwow, Brunoman1990, Bryan Derksen, CDN99, CFCF, CTF83!, Cackerman, Cadiomals, Caknuck, Calimo, Caltas, Camerong, Can't sleep, clown will eat me, CanadianLinuxUser, CanisRufus, Canjth, Carbon arka, Cargoking, Catgut, Cburnett, Ccwoo, Chance Jeong, Charlie123, Charm, Charmander trainer, Cheapshots, Cherkash, Chichui, Childzy, Chizeng, Chodorkovskiy, Chris is me, Chris55, ChrisGualtieri, Christian List, Christopher Parham, Chun-hian, Chunky Rice, CiTrusD, Cielomobile, Citicat, Cjfsyntropy, Ckatz, Clearrise, ClockworkSoul, ClockworkTroll, Cloning jedi, Closedmouth, Cometstyles, CommonsDelinker, Conversion script, CountZepplin, Crazycomputers, Crazydoctor, Creidieki, Crimson30, CrisDias, Crowbarthe1337h4x0r, CryoSagittarius, Cryptographic hash, Crystallina, CuriousOliver, D, DCincarnate, DVD R W, DabMachine, Dacoutts, Danimsturr, Danski14, Dantheman4297, Darry2385, Darth Panda, Darthtire, David D., Dawn Bard, Dawnseeker2000, Db099221, Debresser, Deglr6328, Delta x, Demmy, Dennis Valeev, Deor, DerHexer, DerryTaylor, Dgies, Dharmabum420, Difu Wu, Dina, Discospinster, DivineAlpha, Dmr2, Donarreiskoffer, Dori, Doug swisher, DougS, Dougofborg, Doulos Christos, Download, Dposse, Dracopacoboy, DragonofFire, Drunkenmonkey, Duckdude, Duckttape17, Dylan620, Dylandugan, EMan32x, ESkog, Earthdirt, Ec5618, Edison, Elb2000, Eliz81, Emmanuelm, Emperorbma, Enviroboy, Epbr123, Epingchris, Eric Forste, Eric-Wester, EricAir, Erick.Antezana, Erik9, Erutuon, EryZ, Ettrig, Evercat, Everyking, Extransit, Extremophile, FF2010, FJPB, Fabiform, FaerieInGrey, FallingGravity, Farosdaughter, Fatsamsgrandslam, Fawcett5, Feeuoo, FelisLeo, Fieldday-sunday, Figma, Flatulent tube, Fletcher, Flyguy649, Flyingidiot, Francs2000, Froth, Funkamatic, Funky Monkey, GSMR, GT5162, GTBacchus, Gabbe, Gaby97123, Gadfium, Gail, Gaius Cornelius, Galorr, Galoubet, Gamewizard71, Gareth Wyn, Gasheadsteve, Gato340, GeneMosher, Gensanders, Giftlite, Gilliam, GiollaUidir, GirasoleDE, Gladissk, Glenn, Gogo Dodo, Goodbye Galaxy, Goodnightmush, Gott wisst, Gracenotes, GrahamColm, Greeneto, Grumpyyoungman01, Grunt, Gscshoyru, Gurch, Gyll, HJ Mitchell, HJ32, Hadal, Hagerman, HamburgerRadio, Hamiltondaniel, Hamtechperson, Hans Dunkelberg, Harry491, Hatesschool, Hdt83, Headbomb, Hello32020, Hempfel, Heracles31, Heron, Hippy Sorix, Hobbit13, Hugh2414, Hughitt1, Husond, Hut 8.5, Hv, I be awsome, IP69.226.103.13, IShadowed, IanBailey, Ianbecerro, Icarus, Icedemon, Icey, Illumynite, Imad marie, Imaninjapirate, InsaneInnerMembrane, Iridescence, Irishguy, Istrancis, Itai, Iustinus, Ivanivanovich, Ixfd64, Iztwoz, J.delanoy, JForget, JFreeman, JWSchmidt, Ja 62, JaGa, Jacyanda9, Jag123, Jake, James.S, James086, January, Jaranda, Jarble, Jared81, Jaredhelfer, Jarkeld, Jasujas0, Jauerback, Jaxl, JayW, Jdmirfer, Jeangabin, Jeff G., Jengod, JeremyA, Jerry, Jesse dudezx, Jhinman, Jhon montes24, Jiddisch, Jim, Jimw338, JinJian, Jmameren, Jnb, Joao, Joe Jarvis, Joelr31, John254, Johnuniq, JonHarder, Jonnyboy88, Jordin986, JorisvS, Josh Cherry, Josh Grosse, JoshHoward77, Jrtayloriv, Ju66l3r, Juanjosegreen2, Julesd, Julian Mendez, Juliancolton, Jusdafax, Justin Bailey, Justin Eiler, Jwissick, Jwratner1, KC109, Kaisershatner, Kalogeropoulos, Kandar, Kangie, Kaszeta, Katalaveno, Kateshortforbob, Katieh5584, Kay for kate, Kbh3rd, Kdammers, Keesiewonder, Kehrbykid, Kelseyking, Kelvinsong, Kevin Rector, Kezari, Khargas, KillerChihuahua, Kim Bruning, KingMunch, Kingpin13, Kipala, Kittymew1, Kjlewis, KnightRider, KnowledgeRequire, Koenige, Konman72, Koolokamba, Kosebamse, Kozuch, Kpjas, Krich, Kris33, Kuru, Kylu, L Kensington, LA2, LaMenta3, LadyofHats, Lawstubes, Leafyplant, LeaveSleaves, LedgendGamer, Lejean2000, Leroylevine, Les boys, Leuko, Lexor, Lia Todua, Lightdarkness, Lightmouse, LinDrug, Linuxcity, Little Mountain 5, Littlealien182, Lloydpick, Lordmontu, Lquilter, Lunchscale, Lycurgus, MACHINAENIX, ME IS NINJA, MER-C, MK8, MMA rox, MPerel, MacGyverMagic, MacedonianBoy, Madmaxz, Magnus Manske, Magog the Ogre, Magoscope, Malcolm Farmer, Man vyi, Mandolinface, Mani1, MarcoTolo, Marcus Qwertyus, Marek69, Mario2000, Mark K. Jensen, Marshman, Master of Puppets, MattieTK, Matzman, Mav, Mdmcginn, Meaghan, Medical geneticist, Memenen, Mercenario97, Merlion444, MesserWoland, Methcub, Michael Devore, Michael Hardy, Micheb, Mikesta2, Ministry of truth 02, Miquonranger03, Miranda, Misos, Mitul0520, Mo0, Moeron, Moink, Mouse Nightshirt, Mowgali, Mr. Lefty, MrOllie, MrTranscript, Mxn, Mysid, Mytildebang, N2e, N5iln, NCurse, NHRHS2010, Nabarry, Najzeko, Nakon, Narayanese, Natpal, Natural Cut, NawlinWiki, Nbauman, Nbhatla, Nd State Assosiation, Ndkl, Nehrams2020, NeilN, NellieBly, Nepenthes, NerdyScienceDude, NetAddict, Netoholic, NewEnglandYankee, Nick Bond, Nihiltres, Nmg20, Nmnogueira, Nneonneo, NoisyJinx, Noobeditor, NorbertR, NoriMori, Northfox, NotWith, NuclearWarfare, Nudve, Nunquam Dormio, Ogger181, Ohnoitsjamie, Oleg Alexandrov, Oli Filth, Oliverkeenan, Olrick, Omegatron, Onco p53, Onkelschark, Opabinia regalis, Orangemarlin, OttoMkel, Out slide, OverlordQ, Owenozier, Oxymoron83, PDH, PaterMcFly, Pathless, Patrick, Paully111, Pb30, Pcarbonn, PeepP, Pengo, Pepper, Peripitus, Persian Poet Gal, Pertusaria, Peter Znamenskiy, Phantomsteve, Pharaoh of the Wizards, Phatdan46, Phil153, Philip Trueman, PhilipWest, Piano non troppo, Pichpich, Pile0nades, Pilotguy, Pinethicket, Plantsurfer, Pofkezas, Pooja raveendran, Poopybutts, Popular97, Possession, Possum, Prestonmcconkie, PrincessofLlyr, PseudoOne, Pseudomonas, Psymier, Pusher, Quintote, Quoth, Qxz, R Lee E, R'n'B, RK, Raichu Trainer, Ramsis II, Randomizer3, Ranveig, Raul654, Ravidreams, Razorflame, Rdsmith4, Reach Out to the Truth, Readthesign, Ren799, Renato Caniatti, Reo On, Res2216firestar, Restre419, Rettetast, Rewdewa, RexNL, Reywas92, Riccomario96, Rich Farmbrough, Richwil, Rickpearce, Rjm656s, Rjwilmsi, Rob Hooft, Robert W. A., Robin63, Rocastelo, RodC, Rogper, Romanm, Ronhjones, Rorschach, RoyBoy, Rpgch, Rror, Rsrikanth05, Rustyfence, Ryulong, SMC, ST47, SYSS Mouse, Salwateama2008, Sam Hocevar, Samir, Sander123, Sanfranman59, Sango123, Sarpelia, Savedhewadgh, Sbfw, Scarecroe, SchfiftyThree, SciGuy013, ScienceFreakGeek, Scientizzle, Sciurin, Scohoust, ScottJ, Sean Heron, Selket, Shadowjams, Shalom Yechiel, Shanes, Shantavira, Shim'on, Shinkolobwe, Shirik, ShyHinaHyuga, Sietse, Sir Nicholas de Mimsy-Porpington, Sirex98, Siroxo, Sjakkalle, Skeppy, Sky380, SlightlyMad, Smack, Smartse, Smoggyrob, Snalwibma, Snowmanradio, Snowolf, Soccerstar132, Socrates321, SpaceFlight89, Spancakes2, SpecMode, Specs112, Spellmaster, Spook`, Sputnikcccp, SqueakBox, Squeedlyspooch, SquidSK, Squidonius, Steinsky, Stepa, Stephen Morley, Stephenb, Sterimmer, Stfg, Strangerer, Sugarrush100, Suh004757, Sunrise, SupaStarGirl, Susan Walton, Swimmrfrend97, Syp, Szxd, THEN WHO WAS PHONE?, Tatwell, Taw, Tbhotch, TeaDrinker, TenOfAllTrades, Tennispro427, Terrx, TestPilot, Testaccount rrrr, TexasAndroid, Thatguyflint, The Haunted Angel, The High Fin Sperm Whale, The Last Kilroy, The Missing Hour, The Thing That Should Not Be, The Transhumanist, The undertow, TheRaven7, TheScotsman1987, Thecorduroysuit, Theda, Thedarkestshadow, Theresa knott, Tholly, ThomasTenCate, Threeafterthree, Thue, Tide rolls, TimVickers, Timir2, Timotheus Canens, Timwi, Titoxd, Toejam1101, TomasBat, Topbanana, Tpbradbury, Treesoulja, Trivelt, Troy 07, Tslocum, Tuganax, Tycho, Tyler, Uartseieu, Uncle Dick, Uncle Milty, Unyoyega, Usama042, Useight, Vanished user giiw8u4ikmfw823foinc2, Versus22, Vina, Violetriga, Vogon77, Vsmith, Vvuppala, Vyasa, WahreJakob, Wak 999, WakingLili, Walteryoo93, Warfreak, Wavelength, WeiAMS426, Weregerbil, West.andrew.g, Westerrer, Whosyourjudas, Wiki alf, Wikiborg, Wikidudeman, Wikieditor06, Wikier.ko, Wikilibrarian, WikipedianMarlith, WikipedianProlific, William Avery, Williamb, Wimt, Wmahan, Woland37, Woodardc, Wouterstomp, Wright496, WriterHound, Wsander, Ww12, Wxyz999a, Wyklety, Xelaw, Xp54321, Xymmax, Yamamoto Ichiro, Yarnalgo, Yersinia, Yomamais, Yssha, Yuubinbako, Yyy, Zachary Murray, Zaheen, Zahid Abdassabur, Zaluzar, Zephyris, Zfc89, Zocky, ZooFari, Zzorse, Zzuuzz, Z da Silva, var Arnfjr Bjarmason, , , , 1876 anonymous edits Cell membrane Source: Contributors: 168..., 1exec1, 2sharkalh, 6osama9, 7cg43m, A. Parrot, A.amitkumar, ABF, AThing, Academic Challenger, Access Denied, Adambiswanger1, Adambro, Adenosine, Adrian.benko, Ajraddatz, Akajune, Akanemoto, Akap007, Alan012, Alansohn, Ale jrb, AlexJFox, AlexiusHoratius, Aliyarockzharder, Amkilpatrick, Amp71, Ananthkamath1995, Anaxial, Anchit virmani,, Andres, Andy85719, Antandrus, Apparition11, Arcadian, Arjun01, ArmadilloFromHell, Art LaPella, Arthena, Atethnekos, Avagad2, Avoided, BananaFiend, Banaticus, Bart133, Bassbonerocks, Bencherlite, Bendzh, Bensaccount, Bfigura's puppy, Bgwhite, Biophysik, Bissinger, BitingHobo, Bjarki S, BlahSpecialK, BobbyBoy69, Bobo192, Bogey97, Boing! said Zebedee, Bongwarrior, BorgQueen, BorisTM, Brandmeister, Brauigja, Briannna21a, BrooksMaxwell, BruceBlaus, Bryan Derksen, Burntsauce, Burzmali, CaSJer, Can't sleep, clown will eat me, Canderson7, Carpy singer, Carre, Catfish Jim and the soapdish, Catgut, Cedmudowicz, Ceyockey, Chaldor, Chaos, CharlotteWebb, Chill doubt, Chiros Sunrider, Chiswick Chap, Chris 73, Chris j wood, Chris the speller, Chrislk02, Chronus1029, Cira030, Claire van der Meer, ClickRick, ClockworkSoul, ClockworkTroll, Closedmouth, Collectorben, Conversion script, Coolidays, Cornellrockey, Corpx, Courcelles, Crana, Crohnie, Csutric, Curiouscorey, Cyclonenim, DARTH SIDIOUS 2, DO11.10, DVD R W, DanielCD, Darkmanx806, Darrentcook, Darth Panda, Daughter of Mmir, DavidLeighEllis, Dcandeto, Debresser, Deino Wanthers, Deli nk, Delusion23, DennisDaniels, DerHexer, Dhatfield, Diberri, Dick Mcgee, Discospinster, Disturbedling, Doctorkismet, Domesticenginerd, Donner60,, Doulos Christos, Draeco, Drbogdan, Drphilharmonic, Dss971, Dudelock24, Dwmyers, E-lord, E2eamon, EMT1871, Eastssideboy, Echtoran, Elano, Elassint, Eleassar, Eleassar777, Eleuther, Elia-thomas-zard, Ellywa, Elmyr, Emperor Banh, Enviroboy, Epbr123, Epolk, EricEnfermero, Erpbridge, EuroCarGT, EvelinaB, Evercat, Everyking, Evil saltine, Evy Surender, Exp HP, Explicit, Faizan, Faradan, Fat Ted, Fatal!ty, Fenteany, Ferkelparade, Fermion, Fern91, Fieldday-sunday, Firebrother, Firsfron, Flyer22, Flying Canuck, Foochar, Fraggle81, Frank, Freakofnurture, Fred Bradstadt, Friginator, Fylbecatulous, G3pro, GB fan, GClugo, Gaelen S., Gaff, Gaius Cornelius, Gareth Griffith-Jones, Gd231, Ged UK, Gen. von Klinkerhoffen, Gene-va, Gffkr, Giants27, Giftlite, GillPer, Glagolev, Glane23, GlassCobra, Gludwiczak, Gogo Dodo, GorillaWarfare, Gornly, Graham87, Gwernol, HJ Mitchell, Habj, Hacker312, HaeB, HalfShadow, HangingCurve, Hannah14, HappyCamper, Harvestdancer, HeckXX, Heron, Hodja Nasreddin, Honkbird, HotBabyBoy31097, Howard McCay, Howl5, Hqb, HrishikeshSarode, Hut 8.5, I am One of Many,, I7988414, Ian Yorston, Iburk, IcedNut, Immunize, Incnis Mrsi, Iridescent, IrishFBall32, Isfisk, Itfc+canes=me, Ixfd64, J. Spencer, J.delanoy, JLaTondre, JSpudeman, JSpung, JWSchmidt, JYoung130, Jackelfive, Jackfork, Jackol, Jared81, Java7837, Jaw959, Jebba, Jebus989, Jeff G., Jennavecia, Jeppelbaum, JesseW, Jfdwolff, Jianhui67, Jledgren, JoanneB, Joao, Joehall45, John Cardinal, John D. Croft, JohnFFields, Johnleemk, JohnnyTehUnicorn, JohnstonDJ, Jondel, Jonomacdrones, JordanDeLong, Joseph Rudolf, Joshwalker, Jossi, Journeyman, Jprg1966, Jugyhng, Juliancolton, Jvbishop, Jyril, Jna runn, Kandar, Karol Langner, Katieh5584, Kavanagh21, Kcox101, Keelan1993, Keilana, Kelvinsong, Khukri, Kjkolb, Knute1232001, Kochipoik, Krashlandon, Krellis, Kubra, Kukini, Kuru, KylieTastic, L Kensington, LadyofHats, Lagatapirata, Lahiru k, Laserion, LeadSongDog, LeaveSleaves, Lectonar, Lee726, Leilimo, Lerdthenerd, Levil, Lialono, Lightbulb500, Lights, LikeLakers2, LinDrug, Lir, LittleOldMe, Luckyluke, Lugia2453, Luigi30, Lukas.S, Luna Santin, MER-C, MONGO, Mac Davis, MadGuy7023, Magnus Manske, Mani1, MarcoTolo, Mark Arsten, MarkSutton, Martarius, Masterpiece2000, Materialscientist, Matthewrbowker, MatthiasG, Mav, MaxSem, Maxim, Maxim Razin, Mbtran, McSly, Meaghan, Medical geneticist, Membrane-biologist, Merovigla, Mifter, Mikael Hggstrm, Mike Rosoft, Mild Bill Hiccup, Mnlkpoq, Moreschi, Mr. Lefty, Mrees1997, Mrholybrain, Mrt3366, Mudit7, Munita Prasad, My very best wishes, Myanw, Mygerardromance, Mslimix, N5iln, NSR, Naddy, Nakon, Nasnema, Natalie Erin, Nategraves, NawlinWiki, Nawlinsprincess, Nbauman, Ncmvocalist, Neffyring, Nemu, NewEnglandYankee, Nhandler, Nick, NickBush24, NickGarvey, Nnszhdm, Noctibus, Nono64, Noob244, Northamerica1000, NotAnonymous0, Novadeath69, Nsaa, NuclearWarfare, Nuttycoconut, Nuujinn, O.Koslowski, Obankston, Ocaasi, Onco p53, Ontilu, Oxymoron83, PDH, PFHLai, PGWG, PaddyM, Pb30, Pdcook, Pe-Jo, PerryTachett, Peruvianllama, Peter Karlsen, Peterlin, Pewnedtotal, Pgan002, Pharaoh of the Wizards, Phe, Phgao, Philip Trueman, Phizit, Piano non troppo, Pigglesworth, Pinethicket, Porkrind, Prolog, Pschemp, Pseudomonas, Quadduc, Qwyrxian, Qxz, RA0808, RDBrown, ROFLCOPTERone1!, Racush, Radcen, Radicalrad44, Rainbowjinjo, Raitul hasan nibir, Ranjithsutari, RaseaC, Reconsider the

Article Sources and Contributors

static, Redditor69, Redvers, RenamedUser01302013, RenesmeeEmilyCullen, Reo On, Res2216firestar, Rex1 Wiki*, RexNL, Riana, Rich Farmbrough, Richard001, Ringbang, Rjwilmsi, RockMagnetist, RockSuperStar12, Ronbo76, Ronhjones, Rror, Rswarbrick, Ruwan, Rvlaw, RxS, SMC, SMP, Saaga, Samsara, Sasata, Satellizer, ScAvenger lv, Schmackity, Sean William, Seaphoto, Selket, Sellyme, Sentausa, Serephine, Seto Kaiba, Shanata, Shanes, Shizhao, Skela, Sladeb, Slakr, Sleepaholic, Slightsmile, Smartse, Snow Blizzard, Snowdootle, Soap, Sodium, Soliloquial, Some jerk on the Internet, Someguy1221, Somoza, Soumyasch, Sovbeos, SpLoT, Spamer2000, SpuriousQ, Stegmeister99, Stephenb, SteveChervitzTrutane, Stevertigo, Stickee, Stormie, Stwalkerster, Tainter, Tamil94, Tanvir Ahmmed, Taylordavison, Tbhotch, Temporarily Insane, Tentinator, Terper, Thane, The Duke of Waltham, The Evil IP address, The Irish Mule, The Thing That Should Not Be, TheSeer, Theboss9921, Thingg, Think outside the box, Thisisborin9, Thisismikesother, ThreeDee912, Thunderboltz, Tide rolls, Tidema, TimVickers, Titodutta, Tmmordret, Tobias Bergemann, Tohd8BohaithuGh1, Tom harrison, Tommy2010, Tomnewman12345, Tony1, Torchwoodwho, Tow, Tregoweth, Trevor MacInnis, Tripledot, Tripleshame, Troy 07, Trudeau97, Trusilver, Truthflux, Tsealy6, Tslocum, Ttony21, Tubarun, Twsx, Tycho, Uanfala, Ultimatewall5, Urmomhaha21, VNonesuch, Vary, Vector Potential, Villatorresronaldo, Viridae, Visium, Vrenator, WDM27, WLU, WahreJakob, Walrus068, Wannabekiller, Wasnik, WatermelonPotion, Wavelength, Wayne Slam, Webclient101, Wesleywillis, West.andrew.g, Widr, Wifione, Willking1979, Willybobbyjimbob, Wimt, Windchaser, Wisdom89, Wknight94, WolfmanSF, Woohookitty, WookieInHeat, Wwheaton, Wywin, Xanchester, Xcfrommars, Xcompton, Xxlitleonexx, Yamaguchi , Yaris678, Ygramul, Yousaf465, Ytraere, ZabMilenko, Zachlipton, Zairen99, Zapvet, Zenohockey, Ziphon, Zipzip50, Zocky, Zpb52, 1899 anonymous edits Cytosol Source: Contributors: A3camero, AThing, Alansohn, Albval, Alperen, Andres, Arcadian, Attys, Bensaccount, Bobo192, Bobomarch, Brainmuncher, Brichcja, Chichui, Chris the speller, Circeus, Clicketyclack, ClockworkSoul, Conversion script, Daycd, Dexter's Lab, Diberri, DrFO.Jr.Tn, Drahgo, Drclindsay, Drphilharmonic, Duncan.france, Enchanter, Fraggle81, Fuzzform, Gilliam, Gobonobo, Hectorthebat, Holaroger12345, Hydrogen Iodide, Ioan-Mihai Gale I, Ivan Bajlo, Iztwoz, Jared81, Jcw69, Jesse V., Jncraton, Jsayre64, Jusjih, Kevin Hughes, Khazar2, Korimi, Last Lost, LoneSeeker, Loodog, Lord of the Pit, M1ss1ontomars2k4, MER-C, Marek69, Marqueed, Marshman, Mav, Mgiganteus1, MichaK, Michael Devore, Mike Rosoft, Mike2vil, Miyagawa, MortimerCat, Mquiroz, NPrice, Narayanese, Nbauman, Noneforall, Nunh-huh, Onco p53, PDH, PFHLai, Paine Ellsworth, Petter Trillkott, Quercus solaris, R. S. Shaw, RDBrown, Rama, Revery, Rhys, Rich Farmbrough, Rjwilmsi, RodC, Sanfranman59, Serephine, Shanel, Silvem, Some jerk on the Internet, StAnselm, Staszek Lem, TheAMmollusc, TheLedBalloon, TimVickers, Tombo, Tubarun, VictorianMutant, Wetman, Zundark, 132 anonymous edits Cytoplasm Source: Contributors:, 168..., 1exec1, 2D, 786azad, A3RO, Aaron north, Abc518, Ac352, Ace258, Acroterion, Adambro, Adan, Addshore, Adm820, Adrian.benko, Afctenfour, Ahoerstemeier, AlanD, Alansohn, AlexBlair812, Alexius08, AlexiusHoratius, Alias Flood, Allen3, Allens, Allstarecho, AllyUnion, AlphaEta, Alphachimp, Alphax, Altruism, Ampersand777, Anbu121, AndreaBear1208, Andykinosis, Animum, Antandrus, Anthere, Antonio Lopez, Apers0n, Appeltree1, Arakunem, Aram-van, Arcadian, Artaxiad, Arthena, Ashmt, Atif.t2, Austinpieschel, BD2412, Backslash Forwardslash, Banana04131, Barek, Bassbonerocks, Beetstra, Betamod, Blackcats, Blanchardb, Blood sliver, Blue520, Bluejhon, Bob rulz, Bobo192, Bogey97, Bomac, Bongwarrior, BorgQueen, Breakyunit, Bulba2036, CDN99, CaRzRlIfE, Calmer Waters, Caltas, Can't sleep, clown will eat me, CanadianLinuxUser, Capricorn42, CardinalDan, Cblair1234, Celestianpower, Cellmike07, Chamal N, Chris the speller, ChrisGualtieri, Chrislk02, Chupon, Cirt, ClarkMills, ClockworkSoul, Closedmouth, Cobett123, Cocytus, Cody allen tokarcik, Coffee, CommonsDelinker, Connormah, Conversion script, Coolidays, Cornischong, Courcelles, Crazymonkey1123, Cst17, Csrfly D, Cyclopose1, CzarB, DARTH SIDIOUS 2, DSRH, DVD R W, DVdm, Damnitsme, Daniel Case, Darth Panda, Darth demonbomb, Darthchess, Das Nerd, DasBub, Dawn Bard, Deckiller, Delldot, Delparnel, Denisarona, Dentalplanlisa, Deor, DerHexer, Derg4, Dhodges, DigitalCatalyst, Discospinster, DivineAlpha, Dmuth, Docboat, Doctor Hugh, Dogposter, Donner60, DoubleBlue, DrFO.Jr.Tn, Draeco, Drclindsay, Dspradau, Ducky1278, Dupz, Dynaflow, Dysepsion, Dysfunktion, E Wing, Ealex292, Ebenton, Ed Poor, Edwinstearns, Eleuther, Elia-thomas-zard, Ember of Light, Emw, EnTiKe, Enchanter, Enviroboy, Epbr123, Erianna, Everyking, Evil saltine, FallingRain123, Fama Clamosa, Ferengi, Finngall, Flavaflav1005, Fox Wilson, Funandtrvl, Fuzheado, Fvw, G3pro, GLaDOS, Gear head rsx, Geek302, George The Dragon, Georgette2, Giftlite, Ginsuloft, Gogo Dodo, GrahamColm, GrayFullbuster, Grendelkhan, Grim23, Gruw11, Gscshoyru, Guanaco, Gurch, Guy1890, Halmstad, Harvardprofessor1, Hatch68, Hayabusa future, Heywhatsgoingon, Himynameisnorm, Hordaland, Hornlitz, Htownsocal, Hulek, Husond, Hut 8.5, Hydrogen Iodide, II MusLiM HyBRiD II, IW.HG, Igoldste, Imaglang, Imessedthisup, Indon, Ioeth, Iridescent, IronGargoyle, Isfisk, Isopropyl, Itemirus, J.delanoy, JForget, JLaTondre, JWSchmidt, Jacek Kendysz, Jack007, Jadencampbell3, Jag123, Jarble, Jared81, Javert, Javierito92, Jay-Sebastos, JazzSong, Jcw69, Jdwoodalltx, Jesup, Jim1138, JimVC3, Jimp, Jlfuchs, John Cardinal, JohnArmagh, Jonathan Webley, Josh Cherry, Joshbuddy, Jossi, Josve05a, Juandev, Jusdafax, Kcox101, Kedi the tramp, Keelan1993, Keilana, Kelly Martin, Killiondude,, Kinkreet, Kipu2021, Kirachinmoku, Kirby Raccoon, Knsyknsy, Kopro002, Kosack, Kowey, Kubra, Kukini, LamilLerran, Larth Rasnal, LeaveSleaves, Lee S. Svoboda, Leszek Jaczuk, LightBringer, Lights, Ling.Nut, Lizia7, LoneSeeker, Lugia2453, Lumos3, Lupin, MER-C, MJ94, Magioladitis, Magnus Manske, Majorly, Makeemlighter, MarcoAurelio, MarcoTolo, Marek69, Mariagomez39, Mario777Zelda, Mark Arsten, Mark PEA, MarkS, Martinp23, Master Jay, Materialscientist, Matt Gies, Matthew Yeager, Matthewrbowker, Maxis ftw, Meaghan, Mean as custard, Mentifisto, Messi19, Mi Zhou 324, MichaK, Midgetmunky13, Moneymouse, Monkey Bounce, Monkeymanman, Monty845, Morel, Moreliaboy, MrShoggoth, Mrt3366, Muenda, Munita Prasad, MusikAnimal, Mygerardromance, Mythealias, N.hong.phuc, N5iln, NEIL4737, Nabla, Nakon, Narayanese, Nasnema, NawlinWiki, NeilN, NewEnglandYankee, NickW557, Nicke Lilltroll, Nivix, Nmnogueira, No Guru, Nuhuskers, NunoAgostinho, Nylarathotep, O.Koslowski, Od Mishehu, OllieFury, Omurphy, Oneiros, Ouishoebean, Oxymoron83, PFHLai, Paine Ellsworth, Parriswells, Pat Payne, PatrciaR, Paxsimius, Perfectblue97, Persian Poet Gal, Peter Chastain, Peter.C, PhilKnight, Philip Trueman, Piano non troppo, Pikiwyn, Pilotguy, Pinethicket, Plantsurfer, Plumbago, Pointillist, Prestmo, Psmartt, Ptownsuperbitch, Qwertyasdfqwertyfdsa, Qxz, RJaguar3, Ramaksoud2000, Rami R, Rawling, RedHillian, Res2216firestar, Rettetast, RexNL, Reywas92, Rho, Rholton, Rich Farmbrough, Rjwilmsi, Robertrenn, RockRNC, Ronhjones, RoyBoy, Rrburke, Rtucker913, SUPER ETHAN, Salmar, Sander123, Sangak, Scarian, Scbtex, SchfiftyThree, Sciurin, Scumbag, Serephine, Shadow-Z-Hedgehog, Sharonliang, Shlomke, Shrimp wong, Sing17jazz, Sladeb, Slipwins, Smeazel, Snapish, Snow Blizzard, Snow cat, Sodium, Some jerk on the Internet, Soresumakashi, SpLoT, SpaceFlight89, SpeedyGonsales, Splette, SpuriousQ, StAnselm, Steinsky, Stephenb, Stone, Styrofoam1994, Sunshine4921, SuperHamster, SuperMarioBrah, Sylwia Ufnalska, T-borg, Tameeria, Tangent747, Tanthalas39, Tbhotch, Teles, Template namespace initialisation script, Tempodivalse, Terrace4, Tetigit, TexasAndroid, Thane, The Best Twinkler, The Illusive Man, The Rambling Man, The Thing That Should Not Be, The dissonase, TheCatalyst31, Theda, Thingg, ThumbsOff, Tide rolls, Tim-larry, TimVickers, Timwi, Tiptoety, Tmshates, Tohd8BohaithuGh1, Tolly4bolly, Tom harrison, Tomtom547, Tree Biting Conspiracy, Triwbe, Tubby90, Typhoonchaser, Ugog Nizdast, Ulric1313, Unicyclopedia, UserDoe, Uturnaroun, Velella, Versus22, Vicarious, VictorianMutant, Vinithehat, Vmonkey, Vsmith, WLU, Washington Irving Esquire, Wavelength, Weekssais pblo2, Whale plane, Wikipelli, Will Pittenger, William Avery, Willsey1997, Woohookitty, WriterHound, Wzrd1, X!, Xasz, Xcentaur, Xcl0uds, Xtfcr7, Yahadreas, Yansa, Yintan, Zaheen, Zenithan, ZimZalaBim, Zoicon5, Zorder256, Zzuuzz, , , 1601 anonymous edits Organelle Source: Contributors: 090-chall, 168... DNA edit war, 1pezguy, 2004-12-29T22:45Z,, 28bytes, AVand, ActivExpression, Adenosine, Adrian J. Hunter, Alansohn, Alfie66, Amantine, Anclation, Andre Engels, Andy120290, Andycjp, Anomalocaris, Antionne1, Arcadian, Avoided, BKalesti, Beno1000, Bensaccount, Bernie Sanders' DNA, Bggoldie, Bhumiya, Bidabadi, Billare, Bio geekz, Biologos, Bjarki S, Blake-, Blanchardb, Blaxthos, Bleebie84105, Blue Danube, Bobo192, Boing! said Zebedee, Bomac, Bozartas, Breakyunit, Brian Crawford, CSWarren, Caladont, CanadianLinuxUser, CanisRufus, Capricorn42, Carba, Careless hx, Carhuly, Carmichael, Catgut, Cathardic, Cdcdoc, Chaos, Chaser, Chichui, Chizeng, Chris the speller, Ckatz, ClamDip, ClockworkSoul, Clohse17, Conversion script, Corrigen, Courcelles, Cp111, Cspurrier, Csutric, Csrfly D, DVdm, Daniel5127, Dark Samus, DarkAudit, Darkwind, Darkwind6000, Debresser, Decumanus, Deflective, Deor, DerHexer, Dgw, Dietzel65, Discospinster, DivineAlpha, Dogposter, Doug swisher, Download, Drphilharmonic, Drsrisenthil, Dullhunk, Duncharris, Durova, Dwayne, Edittingdude, Efe, Elapied, Elfboy574, Enochlau, Epbr123, Eribro, Eric-Wester, Evanreyes, Excirial, Extrablue, Faradayplank, Farid2053, Ferengi, Forever Dusk, Fraggle81, Freakofnurture, FreeKresge, G3pro, Gabbe, George W Bush's DNA, Gholam, Giftlite, Gilliam, Ginsuloft, Glassofwateronthecounter, Gogo Dodo, GoingBatty, GrandpaDoc, Gustafave, Guyd, Hadal, Haeinous, Hair, Hal0 g33k101, Halmstad, Harry Reid's DNA, Hello32020, Hotcrocodile, Hurricane111, Hydrogen Iodide, II MusLiM HyBRiD II, IRP, IW.HG, Ilmari Karonen, Ilyanep, Intelati, Iridescent, Ixfd64, J.delanoy, JForget, JaGa, Jackol, Jarble, Jim.henderson, Jmcollier, John Ensign's DNA, John Owens' DNA, John the ripper, John254, Johnny Isakson's DNA, Jon Kyl's DNA, Jon Porter's DNA, Jonathanfu, JonathonSimister, JulianC, Jusdafax, Justinsomnia, KEN SALAZAR'S DNA, KGasso, Kay Dekker, Kazkaskazkasako, Kazvorpal, Kelly Martin, KenEmerson, Kinaro, Kpjas, Kupirijo, Kurtispj, Kville105125, Kwamikagami, Kwiki, L'Aquatique, LadyofHats, LeeG, Leleleleleleleleleleleeee, Lexor, Lilceez, Lir, Livitup, Lordofflame212, Low-frequency internal, Lozeldafan, Lugia2453, Luna Santin, Macaddct1984, Mad Microbiologist, Magioladitis, Magnus Manske, Magog the Ogre, Marcelivan, MarkS, Martial75, Martious, Materialscientist, Mato, Matthew Yeager, Mav, Mentifisto, Mhking, MichaK, Michael Hardy, MichaelBillington, Micromagnets, Middlemanmaster, MidgleyDJ, Midgrid, Mikael Hggstrm, Mike2vil, Misscutie27, Mononomic, Monterey Bay, Mormegil, Mostermann, Mrpepsidrink, Mschel, N2e, Nakon, NawlinWiki, Necessary Evil, Nehrams2020, Neocrypticzero, New Jack Swing, NewEnglandYankee, Ne-n, Nickptar, NilsTycho, OnePt618, PFHLai, Paul Foxworthy, Pauli133, Paxsimius, Pb30, Pepper, Philopp, PhnomPencil, Piano non troppo, Pinethicket, Plindenbaum, Postglock, Princess Clown, Prodego, Proofreader77, R. S. Shaw, RA0808, Rama's Arrow, Razor2988, Rcej, Ready, Realricanboy123, Reaper Eternal, Res2216firestar, Rettetast, Rexkim, Rhd, Riana, Rishaj, Rjwilmsi, Roemmdal, Ronhjones, Scjessey, Seegoon, Senator Palpatine, Sephiroth BCR, Shadowjams, Shakarun1, Shanes, Sharkface217, Shelly berkeley's DNA, Shirik, Shlomke, Skarebo, Skizzik, Slates22, Sludtke42, Smartiger, Snapish, Snigbrook, Snow Blizzard, Snowolf, Soliloquial, Soralin, Spamburgler, Steinsky, Stephenb, Stevenr123, Stwalkerster, Sunrise, Suriel1981, Svick, Sylverfysh, Synchronism, Tangotango, Td321, Ted Steven's DNA, Teknopup, Teles, Template namespace initialisation script, Tentinator, Tetigit, Tgeairn, The Anonymouse, The Thing That Should Not Be, Theccy, Thingg, Tide rolls, TimVickers, Tobias Bergemann, Tohd8BohaithuGh1, Tom Delay's DNA, Tom Lougheed, TomasBat, Tombo, Tomgally, Tommy2010, Totoybrownpogi, TravisTX, Treygdor, Triwbe, Tryptofish, Tyrol5, Vacio, Vanished user 1234567890, Vrenator, WahreJakob, Wavelength, WereSpielChequers, Werieth, Widr, WikiDao, WikiFew, Wikieditor06, Wikipelli, Wondpook, Wouterstomp, Wtmitchell, X!, Yamamoto Ichiro, Yourexhalekiss, ZX81, Zzuuzz, , 843 anonymous edits Cell nucleus Source: Contributors: 069952497a,, 1STstringcorner, 444et, 54gsze4ghz5, A D 13, AMK152, AShin1130, Aaron north, Acdx, Adenosine, Adriaan, Adrian.benko, Afctenfour, Aflumpire, Ahoerstemeier, Alcmaeonid, Alessandro f2001, Alexius08, Alicesteele, Allens, Altar, Anbu121, Andre Engels, Andy120290, AndyZ, Angelicskeleton, Anna Lincoln, Anrnusna, Antandrus, Arakunem, Aram-van, Aranea Mortem, Arcadian, Arthena, Artoasis, Avoided, BBBHHHCCCQQ, Barek, Bart133, Bela Bartoszek, BenJWoodcroft, Bensaccount, Bentogoa, Betacommand, Bethpage89, Bhadani, BigPimpinBrah, BillC, Billygoaty11, Bobo192, Bomac, Bongwarrior, Booksworm, Bragador, Brandonbart, Brettbarbaro, Brighterorange, Brion VIBBER, BruceBlaus, Brumski, Bryan Derksen, Bulldozer1203, CJLL Wright, CWii, Cacolantern, Caltas, Calvwag, Can't sleep, clown will eat me, CanadianLinuxUser, Capricorn42, Casper2k3, Catgut, Cdamama, Celestechang, Centrx, CephasE, Ceyockey, Chaos, Chastityb, Cheapshot202, Chino, Chizeng, Chris.heneghan, Chris857, ChrisGualtieri, Ckatz, ClickRick, ClockworkSoul, Closedmouth, Cmcnicoll, Cntras, Coelacan, ColbeagleTheEagle, Complex (de), Conclark12, Conversion script, Cool3, CopperKettle, Cryptophile, Cureden, DARTH SIDIOUS 2, DMacks, DRHagen, DVdm, Dan Wylie-Sears, Daniel Mietchen, DanielCD, Darkfight, Darth Mike, Darth Panda, Datofm, Dcooper, Debresser, Delldot, Demmy, Den fjttrade ankan, Deor, DerHexer, Dietzel65, Discospinster, Dl400198, Donarreiskoffer, Dosorio2012, DoubleBlue, Dr Aaron, DrMicro, Draicone, Drakemiral, Dreid1987, Drgarden, Drmies, Drphilharmonic, Dycedarg, Dysprosia, ERcheck, Echtoran, Editore99, Edward, Eeekster, Ehaag, Eleassar, Eleassar777, Ember of Light, EnSamulili, Epbr123, EuroCarGT, Everyguy, Evil saltine, Excirial, Fadedlight56, Fang Aili, Faradayplank, Fastily, Fiasco, FishingKing, Flurry1001, Flyer22, Forluvoft, Francine3, Freakofnurture, FrozenMan, Funandtrvl,


Article Sources and Contributors

Fvasconcellos, Fyrael, GAThrawn22, GT5162, Gaff, Gaius Cornelius, Gakusha, Ged UK, Gene Nygaard, Genericmister2000, Genericmister3000, GetAgrippa, Gfoley4, Ghiraddje, Giftlite, GillPer, Gilliam, Gimmetrow, Ginsuloft, Glagolev, GlassCobra, Godlord2, Gogo Dodo, Gracenotes, Graham87, Grahamec, Greg L, Gruzd, Gurch, Gwernol, Habj, Hadal, Hangjian, Hankston, Harrymph, Haydood23, Hazhk, Hdt83, Heero Kirashami, Hello32020, Hollisterfrk1, Hotcrocodile, Hughitt1, Hydrogen Iodide, Hypernite, II MusLiM HyBRiD II, Igoldste, Immunize, IncognitoErgoSum, Insanity Incarnate, Interiot, Irdepesca572, Iridescent, Irishguy, Isaac.holeman, Isfisk, Iste Praetor, IvanLanin, Iztwoz, J.delanoy, JForget, JNW, JWSchmidt, Jacobso4, JamesBWatson, Jamesx12345, Jamison Lofthouse, Jauerback, JavierMC, Jeff G., Jeffrd10, Jesse V., Jesserrro3, Jguard18, JimVC3, Jj137, Jncraton, JodyB, John, Joseph Solis in Australia, Josh Grosse, Juliancolton, Kaushlendratripathi, Kay Krner, Kazkaskazkasako, Kbh3rd, Keilana, Ken Gallager, Kg moin, Khazar2, Khmir2467, Khukri, Kidkidpie, King of Hearts, Kinglz, Kira1366, Klilidiplomus, Kowey, Koyaanis Qatsi, KrakatoaKatie, Krich, Kungming2, Kupirijo, La Pianista, LadyofHats, Lalsingh, Lbthrice, Leafyplant, LeaveSleaves, Leptictidium, Lerdthenerd, Leuko, Lexor, Lightdarkness, Lights, Lir, LittleOldMe, Littleghostboo, Llull, Locke7, Lopini, LovesMacs, LuigiManiac, Luna Santin, Luuva, MER-C, Macaddct1984, Magicwombat, Magnus Manske, Maitch, MarcoTolo, Marcsin, Marek69, Mark Arsten, Materialscientist, Matt Deres, Mattbr, Mayur, Meaghan, Mentisock, Mgiganteus1, MichaK, Michael Devore, Mifter, Mike2vil, Mild Bill Hiccup, Milotoor, Mindmatrix, Mindstalk, MisterSheik, Misza13, Modify, Mononomic, Moreschi, Mr.Bip, Mufka, MusikAnimal, Mutt Lunker, Nad, Nadav224, NawlinWiki, Nbauman, Neonegg, NerdyScienceDude, Neurolysis, NewEnglandYankee, Nick, Nick Number, NightWolf1298, Nihiltres, Nikkimaria, Ninjamatrixking, Nivix, No Guru, Nonagonal Spider, Nono64, Nsaa, O.Koslowski, Ocaasi, Ohsowskisc, Oleksii0, Omega Archdoom, Onebravemonkey, Opabinia regalis, Orphan Wiki, Outriggr, OverlordQ, Oxymoron83, P8ntballer1111, PDH, PFHLai, PM800, Pappucantdancesalla, Parhamr, Paul-L, Paxsimius, Peter, Peter Delmonte, Peter James, Peter-27, Peteruetz, Phantomsteve, Philip Trueman, Piast93, Pierpontpaul2351, Pinethicket, Pip2andahalf, Plantsurfer, Pluemaster, Pluma, Pootang123456789, Posterlogo, Preraraheart, Pro bug catcher, Professer Joseph, Proofreader77, Puchiko, Puffin, Pupster21, Pyrospirit, Quadpus, Quintote, QuiteUnusual, Qwyrxian, R. S. Shaw, RA0808, RadioFan, RandomP, Reaper Eternal, Reconsider the static, RedHillian, Reddy4me1994, Remember the dot, Reo On, Res2216firestar, RexNL, Reywas92, Rich Farmbrough, Richard D. LeCour, Rigby27, Rjwilmsi, Rking36, Rmosler2100, Robert Foley, RobertG, RockfangSemi, RodC, Rorro, Rory096, Rsundby, Rumping, RxS, SEUNGWAN, SMC, SMP, Sam00110101, Sammypkrs, Samsara, Samtheboy, SandyGeorgia, Satellizer, Sbaker100, SchfiftyThree, Schrodingerscat09, Scjessey, Sd2011wiki, Seaphoto, Seegoon, Seejyb, Selket, ServAce85, ShaiM, Shalom Yechiel, Shell Kinney, Shizhao, Shmget, Shoeofdeath, SidneyMorataya, Silvrous, SimonP, Sionus, Sirbonkers, Skelly247, SkyMachine, Slakr, Smartse, Snoyes, Soliloquial, Some jerk on the Internet, Someguy1221, SpaceFlight89, Sparkey01, Spencer, StAnselm, Steinsky, Stepa, Stephenb, Stevo5987, Streetfoo212, Stylodinesh, Summer Song, SuperHamster, Suruena, Syp, THEN WHO WAS PHONE?, Tameeria, Tapir Terrific, Tariqabjotu, Tavilis, Tbhotch, Teentje III, Tekks, Template namespace initialisation script, Tentinator, Terper, Thatotherperson, The Rambling Man, The Thing That Should Not Be, The wub, TheGWO, Thebestofall007, Thine Antique Pen, Thingg, Thomas MacAlister, Tide rolls, TimVickers, Titoxd, Tobias Bergemann, Tombomp, Tommy2010, TonyBallioni, Totoybrownpogi, Tranphuongthuy, Trevor MacInnis, Trusilver, Tryptofish, Two-Sixteen, Tycho, Ugen64, Uncle Dick, User A1, Vald, Vanished user 39948282, Vary, Venullian, Versus22, VictorLucas, Vojtech.dostal, Vossman, Waltpohl, WarthogDemon, Wavelength, Wayne Slam, Webclient101, WereSpielChequers, Whale plane, Widr, WikipedianProlific, Wikipedosucklol2, Wikipedosucklol3, Wikipelli, Will Beback Auto, William Avery, Willking1979, Wimt, Winallfights1991, Winchelsea, Wknight94, Wouterstomp, Xanchester, Yahel Guhan, Yamamoto Ichiro, Yintan, Yug Kansara, Yuyudevil, Zahid Abdassabur, Zfr, , 1329 anonymous edits Nucleolus Source: Contributors: 1exec1, A.R., ABF, ALE!, AShin1130, AThing, Access Denied, Acroterion, Adashiel, Adeleypenguin, AdjustShift, AeonicOmega, Ahoerstemeier, Aidanjohnson12, Aitias, Albertus Aditya, AlexWaelde, Alexd1010101, Alexius08, Almar881, Alpha 4615, Amkilpatrick, AnOddName, Anaxial, Andonic, Andyjsmith, AngelHerraez, Antandrus, AnthonyJ Lock, Antonio Lopez, Aram-van, Arcadian, ArglebargleIV, Art LaPella, Ary29, Astronautics, Aurochs, Avathar, AxelBoldt, Bartledan, BenJWoodcroft, Bensaccount, Bhumiya, BlueAmethyst, Bluefist, Bobjgalindo, Bobo192, Bogenbroom, Bomac, Brhebert, Brianga, Brianlucas, BryanG, Bsadowski1, Bunnyhop11, Bush6984, Butko, Bvluv, CDN99, CWenger, CanadianLinuxUser, Capricorn42, Capt. James T. Kirk, Captain Yankee, Carturo222, Cenarium, Charitwo, Chizeng, ChrisGualtieri, Ckatz, ClockworkSoul, Closedmouth, Cmcnicoll, Conversion script, Cracked acorns, Cremepuff222, DVD R W, Danger, Dangle sniper, DarkArcher, DerHexer, Dgw, Diaa abdelmoneim, Diannaa, Diberri, Discospinster, Dnvrfantj, Doctn, Dogposter, Don Gosiewski, Doom2k6, Download, DragonLord, Durova, DRahier, ENIAC, ERcheck, Elassint, Emre.akaltin, Epbr123, Eric kennedy, Eric-Wester, EricaAnnC, Fadedlight56, Falcon8765, Fan Railer, Fatal!ty, Flyer22, Forluvoft, Fraggle81, Freak104, Fuhghettaboutit, Fyyer, GLaDOS, Ganmedes, Giftlite, Gits (Neo), God Emperor, Gogo Dodo, Graham87, Grantdesrosi, Greatal386, Gurch, Guywithoutaname, Gwernol, Halosix, Hasek is the best, Hdgcfcf, Hedawei21, Hedima, HenryScow, Hersfold, Hmrox, Hxyang, IRP, IceUnshattered, ImperatorExercitus, Iridescent, Ixfd64, J.delanoy, JCA001, JForget, Jag123, Jcmad717, Jdupree1, Jeff G., Jennavecia, Jerry teps, Jmundo, John Cardinal, John254, JohnCD, Jojhutton, JorisvS, Josh3580, JoshuaKuo, Jovianeye, Joyous!, KGasso, Kaarel, Karsyn1222, Katalaveno, Kbeiswen, Keenan Pepper, KeithB, Kerotan, King of Hearts, Kinglz, KirbyRandolf, Kosebamse, Kseferovic, Kukini, Kyng, La Pianista, LadyofHats, Lashbrook, Lastbetrayal, Lateg, LeaveSleaves, Leuko, Liamdaly620, LiquidWater, Lisiate, LizardJr8, Lolmastar, Lordjamz, Luk, Luna Santin, Lupin, Macarenaman, Madscicaly, Magioladitis, Magnus Manske, Mani1, Marcus Qwertyus, Marek69, Markhurd, MartinPoulter, Materialscientist, Matthew Desjardins, McSly, Meaningless, Mememeafsdg, Mentifisto, Mercury, MichaK, Michael93555, Michaelzeng7, Microphonics, Mike.lifeguard, Mike2vil, Milo03, Mindmatrix, Moe Epsilon, Mohawkjohn, Monkeynoze, Mr Stephen, Mrt3366, Msh210, Mygerardromance, NHRHS2010, NawlinWiki, Neelix, NerdyScienceDude, NewEnglandYankee, Newsieluvr, Neznanec, Nihiltres, Nik42, NonDucor, Nonagonal Spider, Noommos, NorwegianBlue, NuclearWarfare, Oddbodz, Ojay123, Ojigiri, OllieFury, Orlandoturner, Orphan Wiki, Oshwah, Oxymoron83, PDH, PFHLai, PL290, Patstuart, PaulGarner, Pbroks13, Pdcook, Pdeitiker, Peasantoid, Petter B-ckman, Phase Theory, PhiJ, Philip Trueman, Pilotguy, Pinethicket, Pjetter, Plumbago, Postglock, Prodego, Pryoidain, Pud milk, Quantumobserver, R'n'B, R. S. Shaw, RDBrown, Radon210, RainbowOfLight, RandomLittleHelper, Raxmus, Redvers, Regancy42, Reywas92, Rich Farmbrough, Richard001, Rjwilmsi, Rm1271, Robomaeyhem, Ronhjones, Rspeer, Rsundby, RunOrDie, RyJones, Rycher88, Seba5618, Shibumichic, Shirulashem, Shlomke, SimonMayer, Sj, Skittleys, Skizzik, Smocking, Smooth O, Sniper120, Snow Blizzard, Snowolf, SouthernNights, Spencer, St3vo, Stallions2010, Sylwia Ufnalska, THEN WHO WAS PHONE?, TR18868, TYelliot, Tassedethe, Tavilis, Tedz1usa, Teh nubkilr, TenOfAllTrades, Tentinator, Tetracube, TexasAndroid, Tgeairn, The Thing That Should Not Be, TheSpoonbender, Thomjakobsen, Thundersnow, Tiddly Tom, Tide rolls, TimVickers, Timotheus Canens, Titoxd, Tolly4bolly, Tranphuongthuy, Travboy123, Trongphu, Tryptofish, Tycho, TypoBoy, Ugen64, Ulric1313, Useight, VUBio Hugo, Vanished User 1004, Vanished user uih38riiw4hjlsd, Vanished user vjhsduheuiui4t5hjri, Velella, Vikky2904, Voltron, Wavehunter, Wayne Slam, Wbickmor, Webridge, Werdan7, WereSpielChequers, Wikieditor06, Wikimachine, Wknight94, WolfmanSF, Woohookitty, WriterHound, X!, Yano, YourEyesOnly, Zargulon, Zfr, Zomno, Zyphrr, Zzuuzz, 1222 anonymous edits Ribosome Source: Contributors:, A8UDI, AAM, Achim Raschka, Acroterion, AdjustShift, AeonicOmega, Agathman, Ahoerstemeier, Aiken drum, Aitias, Akriasas, Alansohn, Ale jrb, Alexius08, Alexllew, Alfie66, Alksub, Amatulic, Ananthkamath1995, Andre Engels, Andrewrp, Andy pyro, Andy4789, Anomalocaris, Anonymous Dissident, Antandrus, Arakunem, Aram-van, Arcadian, ArchDaemon, Arkuat, Arnoldlcl, Atif.t2, Az1568, Aznshark4, Banpei, Banus, BarretB, Bart133, Bendover12345, Bensaccount, Benzenetoaster, Betacommand, Billybutterworthreborn, Biodoc546, Blaxthos, Blood sliver, Bluesquareapple, Bobo192, Boppet, Brambleclawx, Branddobbe, Breckp, Brianmurphy22, Brim, Burntsauce, CKlunck, Caladont, Can't sleep, clown will eat me, CanadianLinuxUser, Captaincollect1970, CardinalDan, Carstensen, Cela, Cerealkiller13, Chaos, CharlesC, Chrisahn, Chrishmt0423, Christian List, ClarkFreifeld, Cless Alvein, Climax Void, Closedmouth, CommonsDelinker, Connormah, Conversion script, Cph3992, CryptoDerk, Crystallina, Cstillabower, Cypher3c, Czernilofsky, D, D. Recorder, DMacks, DVD R W, DVdm, Dan100, Danny B-), Darth Panda, Dashed, Dcrjsr, Debresser, Delta G, DenLianda, DerHexer, Dfrg.msc, Dgw, Diberri, Discospinster, Dkasak, Dmanning, Dogposter, Dominus, Donarreiskoffer, DopefishJustin, DragonflySixtyseven, Drgarden, Drphilharmonic, Duhmutton, EdwardLawrence, Electronsaregreen, Elewton, Elfalem, EmadIV, Enviroboy, Epbr123, Eric-Wester, Erik9, Euchiasmus, Euland, Everyking, Evilninja180, Excirial, FallingGravity, Felix Tritschler, Fingerz, Firsthuman, Flameviper, Foxj, Freakofnurture, Frickson, FuelWagon, GRAHAMUK, GT5162, Galorr, Gen. Quon, Gene Nygaard, Geoking66, Giftlite, Gilliam, Gimboid13, Glane23, Gogo Dodo, Gould363, GraemeL, Graham87, GrahamColm, Greensburger, Guillom, Gurch, Gwernol, Gzkn, Hacker312, Hadal, Halmstad, HamburgerRadio, Hangjian, Have fun with this, Hersfold, HiDrNick, Hichris, Hodja Nasreddin, Home Row Keysplurge, Hu12, Hut 8.5, Hydrargyrum, Hyyfgk101, Igodard, Igoldste, Illia Connell, Intelligentsium, Ion496, Ipatrol, Ipodamos, Iridescent, Isfisk, Isnow, J.delanoy, JForget, JWSchmidt, Jack the Stripper, JackWasey, Jackollie, James086, Jaredwinkler, JavierMC, Jayreimer, Jbening, Jd Tendril, Jdclevenger, Jebus989, Jed 20012, Jimp, Jjalexand, Jklin, Jls043, Jmschrad, Joao, John Mackenzie Burke, John254, JohnArmagh, JohnyDog, JonMoulton, Jones1337, Jorge Stolfi, Jrtayloriv, Julesd, Julian Mendez, Kaarel, Kanags, Kaobear, Karin D. E. Everett, KawaiiApocalypse, Kazkaskazkasako, KeithB, Kf4bdy, Khoikhoi, Kingpin13, KnowledgeOfSelf, Kralizec!, Kukini, LadyofHats, Lalawasabi, Lambmeat, LcawteHuggle, Lexor, LikeLakers2, Lir, Little Mountain 5, Lproven, LukeGoodsell, MER-C, MaNeMeBasat, Magioladitis, Magnus Manske, Majorly, Mandarax, Mani1, Mantha.satish, Master of Puppets, Math Champion, Mattb112885, MattieTK, Mauror, Maury Markowitz, Max, McSly, Meredyth, Michael Devore, MichaelBillington, Michaelfavor, Mike2vil, Mikemoral, Mishlai, Misterstark, Mjpieters, Modeha, Mogism, Mr Stephen, Mr. Wheely Guy, MrFish, Munita Prasad, Mushin, Mxn, NCurse, NHRHS2010, Nakon, Narayanese, NawlinWiki, Nbauman, NerdyScienceDude, Neurolysis, Never give in, Newone, NickCT, Nihiltres, Nilfanion, Nina, Nonagonal Spider, Novangelis, Nsaa, Nubzor, NuclearWarfare, Nwbeeson, Omicronpersei8, Orthank, Otvaltak, OverlordQ, Oxymoron83, PFHLai, PVSpud, Pablhern, Papa November, Pascal.Tesson, Pdcook, Pekaje, Petercoccusfuriosus, Peteruetz, Petri Krohn, Pgan002, Philip Trueman, PiRSquared17, Piano non troppo, Pinethicket, Plantsurfer, Plasmid, Ppgardne, PrestonH, Quinsareth, Quintote, Qxz, RFerreira, RJCoppin, ROFLCOPTERone1!, Radioactivebloke, Rajesh822, Rama's Arrow, RandomStringOfCharacters, Razorflame, RelentlessRecusant, Res2216firestar, Rettetast, Rich Farmbrough, Rjwilmsi, Rmosler2100, Rodhullandemu, Romanm, Rory096, Rotational, RoyBoy, Rrburke, Ryulong, SAVE US.L2P, Sanjeev.singh3, Satish suryan, Scientific29, Scirocco6, Sciurin, Scorpiuss, Scwerllguy, Sean William, Severa, Shanes, Sheehan, Sir Vicious, Sirtywell, Sj, Sky380, SmilesALot, Smilesfozwood, Snafflekid, Some jerk on the Internet, South Bay, SpaceFlight89, Speciate, Staticd, Steinsky, StephenBuxton, StereoTypo, Stoive, Strasserk08, Sukkoth Qulmos, Sunrise, Syko66613, Tamiasciurus, Tanaats, Tavilis, Taw, Tdk327, Techman224, Template namespace initialisation script, Terry Longbaugh, TestPilot, Thatwchduznotfly, The Rambling Man, The Thing That Should Not Be, The undertow, ThePointblank, Themadness, Thistheman, Tide rolls, Tim-larry, TimVickers, Tiptoety, Tom Lougheed, Tpbradbury, Trevorloflin, Treyd500, Tristanb, Twas Now, Twsx, Tycho, Tyler, Ugen64, Ukexpat, Unconcerned, Universewik, Unyoyega, Utcursch, Vishnava, Vokesk, Vossman, Vrenator, Waffles209, Walterdavidsmith, Warriorsrule2478, Warrush, Wavelength, Westie28, Wetman, Wik, Wikianon, Wikibofh, Wikipelli, Will Bradshaw, WillowW, WriterHound, Wtmitchell, Xaraikex, Xaxx, Xdenizen, Xnurfz, Yamamoto Ichiro, Yogi de, YuanH, Ywith, Zephyris, Znkp, ZooFari, Zzuuzz, 1175 anonymous edits Vesicle (biology and chemistry) Source: Contributors: %xxtrackingcookiexx%, 168..., A412, Achowat, Adambiswanger1, Addihockey10, AlB, Alansohn, Alexdubr, Amr94, Anafar, AnnaP, AquamarineOnion, Aram-van, Arcadian, Audriusa, Aviados, Ayacop, BabbaQ, Banus, Ben Robert, Bender235, Bensaccount, Blaxthos, Boing! said Zebedee, CanadianPenguin, CanisRufus, Centrx, Chaos, Clone89, Cmdrjameson, Connormah, Conversion script, Courcelles, Cyclonenim, DARTH SIDIOUS 2, Dan Gluck, Daycd, Demitsu, DerHexer, Diberri, Difu Wu, Discospinster, Dmontesano, Dogposter, Donner60, Durova, Eleassar777, Epbr123, Ericdiluccio, Fenteany, Fieldday-sunday, Flyguy649, Flyingtoaster1337, Foobar, Forty Seven Nine, Fryed-peach, GB fan, Giftlite, Gurch, Gyll, Hadal, Hakan Kay, Hallenrm, HamburgerRadio, Hattiey, Heron, Hodja Nasreddin, Jackfork, Jehochman, Jesse V., Jet the Nerd, Jfurr1981, Jguk, Jj137, John254, Jolivio, Jwadeg, Kinglz, Kirankumar1234, KoshVorlon, Kristenhug, Lexor, Lir, Lucky 6.9, Lugia2453, MCGrief, Magioladitis, Magnus Manske, Mark Arsten, Martarius, Martin451, Materialscientist, Mcmillin24, Mderezynski, Mean as custard, Mendaliv, Methcub, MichaK, Mikael Hggstrm, MisterSquirrel, My very best wishes, Mysterytrey, Narayanese, Nathan, Nilfanion, Nipisiquit, Nmedard, Oddbodz, OlEnglish, PFHLai, Patstuart, Phantomsteve, Philip Trueman, Pinethicket, Plantsurfer, Proofreader77, Qtnguyen92683, RDBrown, Rich Farmbrough, RickK, Rittard, Robert M. Hunt, RockMagnetist, Rotational, Rozzychan, SMC, Scoops, Seaphoto, Shadowjams,


Article Sources and Contributors

Skizzik, Sky380, Slon02, Smartse, Sminthopsis84, Specs112, SpeedyGonsales, Spencer, SriMesh, Sriharsh1234, Steinsky, Stepa, Stevage, Stwalkerster, TJJFV, Template namespace initialisation script, The Anome, The Utahraptor, TheGrimReaper NS, Thexmanlight, Thingg, Tide rolls, TimVickers, Tpbradbury, Travis, Traxs7, Tryptofish, Ukexpat, Unused000701, WLU, Wavelength, WriterHound, 395 anonymous edits Endoplasmic reticulum Source: Contributors: .:Ajvol:., 168..., 23th, 27jacob27, 6r6r6muyr6uh, 97198, ;jdfnudiudsacfjamcaroueafh;ndjk;h, A.amitkumar, Aaron Schulz, Aaron98990, Aaw37, Abc518, Academic Challenger, Acather96, Achim Raschka, ActivExpression, Adrian J. Hunter, Adrian.benko, Ahoerstemeier, Aleenf1, Alemily, Alex.tan, Alice D'Rozario, Alksub, Allen3, Allstarecho, Almar881, AlphaEta, Altar, Anaxial, Andrewpmk, Andy M. Wang, Andy120290, Antandrus, Anthere, Arcadian, Arjun01, Arnavchaudhary, Arnd Klotz, Ayrenz, AznBurger, Beaujohnson80, Bemoeial, Benbest, Bencherlite, Bender235, Bensaccount, Besenk, Besieged, BillyPreset, BimJin209, Biomaxan, Blechedbutthole, Bluemoose, Bobo192, Bomac, Boogerpatrol, Brandonbb13, Brianpie, BruceBlaus, CalculatorChad, Calmer Waters, Can't sleep, clown will eat me, CanadianLinuxUser, Canderson7, Catbar, Ceyockey, Chamal N, Chibibrain, Chris Mason, ChrisGualtieri, Cjb88, Ck lostsword, Closedmouth, Cntras, Coemgenus, Conversion script, CopperKettle, Crad0010, Creasy2001, Crxs, Cryptic, D Dinneen, DBigXray, DMacks, DRosenbach, DancingPenguin, Danfa1971, Daniel Mietchen, DanielCD, Danielkueh, Danski14, Darry2385, Darylgolden, DavidLeighEllis, Davidfg, Db099221, Dcooper, DennyColt, DerHexer, Dgw, Diberri, Dipics, Discospinster, Djadvance, Donner60, Doug swisher, Dr Zak, Dragonchat20, DragonflySixtyseven, DroEsperanto, Drphilharmonic, Dsbjd, E Pluribus Anthony, Edward, Egonw, Eleassar, Electriccatfish2, Eleuther, EmadIV, Emufarmers, Eric Forste, Eupedia, Excirial, Exert, Exocto, Fang Aili, Featherfin, Fieldday-sunday, Finlay McWalter, Fitzwilliam, Fixthisquestion, Flockmeal, Flyer22, Flyguy649, Francs2000, Frankg, Frazzydee, Fredrik, Freeradster, FreplySpang, G3pro, Gator221, Giftlite, Gigabyte88, Gigemag76, Gilgamesh he, Gimmetrow, Ginkgo100, Ginsuloft, Glacialfox, Gobadape84, Godlord2, Gogo Dodo, Goodnightmush, Grunt, GullibleKit, Gurch, Gwernol, Halmstad, Hamamelis, Have fun with this, Hdt83, Hobson, Hodja Nasreddin, HoodedMan, HumphreyW, Hydrogen Iodide, Ianblair23, Iancrose, Iliketoalter, IlyaV, Iridescent, Isfisk, Isis, J.delanoy, JForget, JWSchmidt, Jack007, Jacward97, Jared81, JedOs, Jeffrd10, Jim1138, Jmarhee, Jncraton, Joehall45, John Price, John254, JohnWittle, Josh Grosse, Jpkoester1, Jtkiefer, Juandev, JungleAnn, Jusdafax, Jwissick, Jwratner1, Kablammo, Katalaveno, Kbdank71, Kelvinsong, Kenaycock, Kevin.cohen, Kiarrarowe, Kkmurray, KnowledgeOfSelf, Knulljar en din fidda, Kostja, Koyaanis Qatsi, KrakatoaKatie, Krich, Kurykh, Lalaloopsies, Lamaybe, Laramienicole, Larry_Sanger, Lexor, LibLord, Lights, Lir, Littleghostboo, Lookimscared, Lordpepsi, Loriendrew, Lradrama, Lugia2453, Luk, Luke Hayden, Luna Santin, M A Mason, MER-C, Mac Davis, Macaddct1984, MadGuy7023, Magnus Manske, Malcolm, Manfi, Maniesansdelire, MaraNeo127, Mark Arsten, Marshallsumter, Materialscientist, Mavman041, Mcy jerry, Megaman en m, Mehrunes Dagon, Meters, Mewasul, Mgiganteus1, Microtubules, Middenface, MidgleyDJ, Mikael Hggstrm, Mike2vil, Millermk, Mmm donuts, Moe Epsilon, Moeron, Moliphant, Mooseofshadows, Mproncace, Mr Stephen, Mrt3366, Muralidharan le, Mushroom, MusikAnimal, Mxn, NPrice, Nappyrootslistener, Naval Scene, NawlinWiki, Nburky, NewEnglandYankee, Nick BN1, Nick2736, NightWolf1298, Nilfanion, Nkayesmith, Nmnogueira, Nneonneo, No Guru, Nonagonal Spider, Nrsmoll, Nyssahyo, Ohwell32, Ondenc, Onorem, Oxfordwang, PDH, PFHLai, Palexandridis, Pancakewafflezslayer101, Paul August, Pbroks13, Peachypoh, Pepper, Perlygatekeeper, Petrus brasiliensis, Philip Trueman, Pinethicket, Plantsurfer, Plastikspork, Prolog, Pwbrooks, Quaestor, Quebec99, Quietust, Qxz, R, R. S. Shaw, RB972, RJaguar3, Racerx11, Raquel Baranow, Rdsmith4, Reatlas, Rednblu, Rjwilmsi, Rodlangway, Romanm, Russot1, SS Lindsay10 Ss, Sam Mirkin, Samir, Sampo Tiensuu, Sango123, Saturation2, ScAvenger lv, ScottSteiner, Sean.hoyland, Seaphoto, Sedmic, Sennard, Sentausa, Seren-dipper, ShadowDemonsRevenge, Shadowjams, ShakingSpirit, Sharkface217, Shaun, Sherylmartinez11, Shizhao, Shrimp wong, Sietse Snel, Siroxo, Snow Blizzard, Snowmanradio, Solo Owl, Some jerk on the Internet, Sortior, Sovbeos, Spartan, Spaully, Speedyboy, Sschles1, Stable attractor, Steel, Steinsky, Sterling32157, Stizz, Super48paul, Swatjester, Sxim, Taabouzeid, Tarotcards, Tbhotch, Tekana, Telfordbuck, Template namespace initialisation script, TenOfAllTrades, Tentinator, Thane, The High Magus, The Phoenix, The Thing That Should Not Be, The cookie monster, TheGerm, Thececil, Tholme, Thundersnow, Tide rolls, TimVickers, Tiptoety, Tolly4bolly, Tomos ANTIGUA Tomos, Trendsettr, Trlovejoy, Trudyomara, TwoTwoHello, Tycho, Tyler, User24, Vacation9, Vanished user 9i39j3, Vanished user ikijeirw34iuaeolaseriffic, Vertium, Vintblack, Walrus068, Waltpohl, Warakawa, Wasell, Wattsu42, Wavelength, White Shadows, Widr, Wikipelli, Wimt, Wknight94, Xavid, Xdenizen, Xelgen, Yamamoto Ichiro, Youssefsan, Zachlipton, Zeroro, Zhuuu, Zidanie5, Zouavman Le Zouave, Zzuuzz, ^demon, , 1225 anonymous edits Golgi apparatus Source: Contributors: 069952497a, 9258fahsflkh917fas, A Stop at Willoughby, A little insignificant, Aaronatwpi, Aceexmee, Adambiswanger1, AdjustShift, Adriaan, Adrian J. Hunter, Adrian.benko, AdultSwim, Aff123a, Ahoerstemeier, Airplaneman, Alansohn, Aldaron, Ale jrb, Alex Bakharev, Allstarecho, Almar881, Alphachimp, Amitch, Anafar, Andy85719, AnthonyQBachler, Arcadian, ArielGold, Arthena, Astrale01, Astroview120mm, Avicennasis, Avoided, AznBurger, BRUTE, Bad edits r dumb, Barak Naveh, Battlebison, Benjohnson81, Bensaccount, Bigslow123, BillC, Bmicomp, Bobo192, Boghog, BombSaddam, Bradmontague, Brasilianbabii3, Brim, BruceBlaus, Bsadowski1, Bsherr, Bushcarrot, CBFan, CLW, Cache22, Calabe1992, Calvin 1998, Can't sleep, clown will eat me, CanadianPenguin, Carmichael, CatherineMunro, Chamal N, Chefyingi, Chevalier00, Chibibrain, Chitomcgee, Cholmes75, Chris Capoccia, Chris is me, ChrisGualtieri, Chrislk02, Chupon, Chuunen Baka, Cjb88, ClockworkSoul, Closedmouth, Cmerca678, CommonsDelinker, Conversion script, Coolkid34, CopperKettle, Cpl Syx, CrasherX, Crohnie, Cyanidethistles, Cyfraw, Cynical, D, DARTH SIDIOUS 2, DO11.10, DVD R W, Dan Wylie-Sears 2, DancingPenguin, Daniel Newby, Danny, Dasyornis, Dawn Bard, Dcflyer, Ddsoloman5000, DeadEyeArrow, Debayudh Chowdhury, Delirium, Dfrg.msc, Dfunk58, Dhawk1964, Diberri, Discospinster, Dithridge, Dmr2, Dogposter, Dr.michael.gleason, DragonflySixtyseven, Durova, Dycedarg, ERcheck, ESkog, East718, Eeekster, Einhov, Eirik Wix-e Svela, El C, Encephalon, Epbr123, Esanchez7587, Ettrig, Everyking, Expertathistory, FF2010, Fingerz, Finlay McWalter, Fraggle81, Fujitofu, Funkypeace, F, Gail, Giftlite, Gilliam, Glacialfox, Glane23, Glen, Gnemnes, Gobonobo, Goldkingtut5, Golfandme, Goodvac, GraemeL, Grafen, Gsp, Gwernol, Hadal, Hallows AG, Hamiltondaniel, Hardhits103, Helenabella, Heliac, Hello32020, Hellokitty45654, Herostratus, HiDrNick, Hmains, Hyperfusion, Iain99, Ikiroid, ImperatorExercitus, Inferno, Lord of Penguins, Inka 888, Intelligentsium, Interveinious, intertwined, Ipodamos, Iridescent, Isaac.holeman, Itemirus, Ixfd64, J.delanoy, JForget, JLaTondre, JSpung, Jab843, JackSparrow Ninja, James086, Jared81, Jeffq, Jeremyb, JerryJia, Jesselenton, Jfurr1981, John Cardinal, John254, JohnnyB256, Josh Grosse, Jovianeye, Jprg1966, Jsharpminor, Julesd, Juliancolton, Jumbuck, Jusdafax, Jvbishop, Jwissick, Kalaiarasy, Kandar, Karafias, Katalaveno, Kazvorpal, Kdawgparker, Keegscee, Keelan1993, Kehrbykid, Keilana, KeithB, Kelvinsong, Kendrick7, Khukri, Kiarrarowe, King of Hearts, Kingpin13, KoshVorlon, Koyaanis Qatsi, KrakatoaKatie, Krista10014, Kurzon, Kuyabribri, L Kensington, LOLMAN89, La goutte de pluie, LadyofHats, Laundry, LeaveSleaves, Lee-Lee 44, Lehtv, Leon Byford, Lexilovesyou!, Lexor, LibLord, Lights, Lijnema, Lir, Logan.Phospholipid, Lost.goblin, Luke Hayden, MER-C, MPerel, Madden NFL 21, Makemi, Marek69, Mark Arsten, Marshall Williams2, Martynas Patasius, Materialscientist, MattSal, Mav, Maximus Fingolfin, Maximusthaler, MaximvsDecimvs, Mercredi-Soir, Methcub, Midom, Mifter, Mike Christie, Mike Dill, Mike.lifeguard, Mike2vil, Mikemoral, Mikeo, Million Moments, Miquonranger03, MithrandirAgain, Moeron, Monselepoo, Mxn, Mygerardromance, N419BH, Najibeltecle, Nepenthes, NewEnglandYankee, Nickth3ginger, Nicolas Barbier, Nihiltres, Nilfanion, Nishkid64, No Guru, NorsemanII, Northamerica1000, Nsaa, O.Koslowski, Ojay123, Orfen, Otherone, PFHLai, Pb30, Pbroks13, Peasantoid, Pedro7AC4, Peoplefussy, Persian Poet Gal, Pfranson, Pinethicket, Pisanidavid, Plantsurfer, Pradhipta, Prolog, Quantumobserver, Quarty, Quercus solaris, Quintote, Qwerty Binary, Qwyrxian, Qxz, R. S. Shaw, RandomStringOfCharacters, Reach Out to the Truth, Regibox, RenamedUser01302013, Renato Caniatti, Renegade Replicant, Res2216firestar, Rettetast, RexNL, Reywas92, Ribonucleic, Rich Farmbrough, Richard1990, Rjwilmsi, Rmosler2100, Robomaeyhem, Romanm, RoyBoy, Rrmsjp, Rubicon, RvandenBerg, Rymich13, SMC, STANE, Salsagirl392, Samwb123, SaviorSix, Sbmehta, ScAvenger lv, Schutz, Scientistaryaman, Sciurin, Scohoust, Selket, Serephine, Shell Kinney, Shlomke, Shoeofdeath, Shoessss, Sionus, Sir Nicholas de Mimsy-Porpington, Siroxo, Skarebo, Skizzik, Sladen, Slon02, Smartse, Snow Blizzard, Sodium, Some jerk on the Internet, Sonia, Spikey115, Splash, SpuriousQ, Srielity, Starwiz, Steinsky, Stephen Gilbert, Steve2011, Stifynsemons, Suh004757, SuperHamster, Supersammyboy, TamCaP, Tameeria, Tbhotch, Teamsc, Teles, Tellyaddict, Template namespace initialisation script, Temporaluser, Tentinator, Tgeairn, The Rambling Man, The Thing That Should Not Be, TheRedPenOfDoom, Thernlund, Think Fast, Thorwald, Thundersnow, Tiddly Tom, Tide rolls, TigerShark, Tim2day, TimVickers, Tktktk, Tlim7882, ToastyMallows, Tom harrison, Tonei, Trakuet, Tregoweth, Triona, Triwbe, Truthflux, Tybeedoo, Tycho, Tyrol5, Ugen64, Ugur Basak, Uncle Dick, Unicyclopedia, Unioneagle, UrsoBR, User27091, VKemyss, Vancouver Outlaw, Vanished user 19794758563875, Vibitz, Vinnie1337, Vipinhari, VirtualDave, Vpzom, Vrenator, WadeSimMiser, Waggers, Warfvinge, Warrior4321, WarthogDemon, Wayne Slam, Webclient101, West.andrew.g, Whcodered, Where next Columbus?, Whiskey in the Jar, White Ash, White Trillium, Wi-king, Wiki alf, Wikiman211, Wikipedianerd123, Wikipelli, William Avery, Wiseoldfish, Wknight94, Wl219, Wolfenight, WookieInHeat, Wysprgr2005, Xanchester, Xhaoz, Yamamoto Ichiro, Yapper1200, Yelyos, Yordirosales, Youssefsan, Yuckfoo, Yunshui, Zap Rowsdower, Zfr, Zink Dawg, Zzuuzz, , , 1456 anonymous edits Cytoskeleton Source: Contributors: 12 Noon, 168..., 18th, 23th, 28421u2232nfenfcenc, A Softer Answer, AdamWeeden, Alansohn, Ale jrb, Alex.tan, Alexei Kouprianov, Allangmiller, Alphachimp, Amaltheus, Amkilpatrick, Andreipro87, Andrewjlockley, Aram33, ArazZeynili, Arcadian, Arcette, Archelon, At3rg0, Backslash Forwardslash, Banus, Barneca, Bballoakie, Bellerophon, Bensaccount, Bernster1, Bfigura's puppy, Bjarki S, Blackbooks, Blue Danube, Blueghetto19, Bobo192, Bomac, Bowlhover, Brim, Bryan Derksen, Bubbachuck, CTF83!, CWii, CardinalDan, Chaosfishofgreen, Chill doubt, ChrisHodgesUK, Chromaticity, ClockworkSoul, Coffee, CommonsDelinker, Cpl Syx, Cyberpower678, DRTllbrg, Damiens.rf, Daniel Mietchen, Darth Panda, Daven200520, David Latapie, DerHexer, Dlae, DoktorH, Dono, DrNixon, Dreadstar, Dupz, Edgar181, Eleassar, Epbr123, Excirial, Fenteany, Fieldday-sunday, FreplySpang, Garffunkel, Gene Nygaard, Gexivan, Giftlite, Ginsuloft, Glenn, GoShow, Gobbleswoggler, Grayshi, Grouf, Grunt, Gsp8181, Gurch, Habj, Hangjian, Hello71, HenryScow, Heron, II MusLiM HyBRiD II, IRP, Icelight, Igibbons, Imaninjapirate, IronGargoyle, Isnow, Ivan Denisov, JWSchmidt, Jackol, Jared81, Jesse V., Jncraton, Johndheathcote, Johnuniq, Jojhutton, Jschnur, Jusdafax, Kablamo2007, Keilana, KnightRider, KnowledgeOfSelf, Krotera, Kupirijo, Kuru, L33matthews, LOL, Lando5, Lee M, Lir, LittleT889, Littlebug, Lord of Antria, Lottamiata, LovesMacs, Lugia2453, M1ss1ontomars2k4, MER-C, Maniago, MarcoTolo, Marek69, Marshallsumter, Martious, Mav, Michael.Clerx, Mikael Hggstrm, Mike2vil, Miquonranger03, Mjpieters, Mllyjn, Mojo Hand, MusikAnimal, N5iln, Narayanese, Nasnema, NawlinWiki, Neoroy5, Ok1210111111, Oldekop, Omgsockmonkeys!, Onco p53, P'tit Pierre, PFHLai, Pakaran, Para, Pauli133, Perlygatekeeper, Perseonn Balthasaar, Philg88, Pinethicket, Poofinger1236, Pseudomonas, ReDeHydrate, Reo On, Reywas92, Richwil, Rjwilmsi, Rls, RoyArnon, RoyBoy, Rrburke, S11xtreme, Saboetage, Sam Hocevar, Sarai.123, Saranghae honey, SchfiftyThree, Science4sail, Sean.hoyland, Serephine, Shadowjams, Shoaler, Shoeofdeath, Shusane, SimonP, Skrewler, Smilingangsta elmo, Splette, SteelRegn, Stepa, Stwalkerster, Susfele, SwisterTwister, Szquirrel, TAKEN00, THEN WHO WAS PHONE?, Tbc2, Teammm, Techman224, Thane, The Thing That Should Not Be, TimVickers, Tiptoety, Tolly4bolly, Trillo333, Triolysat, Triwbe, Tsyuen, Tycho, Unionhawk, Vermiculus, Versus22, VictorianMutant, Vlmastra, WeigelaPen, WelshTaliesin, Wikijens, Wimt, Winnen209, Wisebridge, Wknight94, Wolfgang Kufner, Wywin, X esta x, Yerpo, Yossiea, ZabMilenko, Zaheen, ZayZayEM, Zfunction, Zocky, Zundark, 622 anonymous edits Mitochondrion Source: Contributors: 168...,, A-giau, A30382, Aaron Schulz, AbigailAbernathy, Across the miles, Adenosine, AdjustShift, Ado, Adriaan, Adrian.benko, Aeioun, Ahaffa, Aircorn, Aitias, Alansohn, Alcmaeonid, Algumacoisaqq, Allen4names, AlphaHelical, Alumunum, Amarrg, Anaraug, Anclation, AndyZ, AnkhMorpork, Anomalocaris, AnonMoos, Anrnusna, Antandrus, Apeckwiki, Apollo2699, Apotheosis247, Appraiser, Arbitrarily0, ArbitraryConstant, Arcadian, Arey051012, Aronlee90, Arthur Holland, AshLin, Ashmoo, Ashnard, Asukite, Atakdoug, Axeman89, Axl, Ayesha Verma, Az1568, BD2412, BRUTE, Banus, Barack Obama's DNA, BarretB, Beave187, Belinrahs, Bellerophon, Ben-Zin, Benbest, Bencherlite, Bender235, Beno1000, Bensaccount, Bernard192, Bernopedia, BerserkerBen, Bgold4, Bhadani, Bhonga, Bigdottawa, Biologos, Bjarki S, Blowdart, Bobo192, Boccobrock, Bogdangiusca, Bongwarrior, Bookworm2323, Bragador, Brambleclawx, Brian the Editor, BrightStarSky, BrokenSegue, BruceBlaus, Bryan Derksen, Btilm,


Article Sources and Contributors

Bubamara (usurped), Bullzeye, Burner0718, C6541, CDN99, Callanecc, Caltas, Can't sleep, clown will eat me, CanadianLinuxUser, Canderson7, CanisRufus, Canzhiye, Captain-tucker, Carmmann, Carpy singer, Carstensen, Cathardic, CattleGirl, Cbrown1023, Cburnett, Ceyockey, Cheifsguy, Chip123456, ChrisGualtieri, Chrislk02, Chrissyallen92, Christian75, Chronulator, Chyeburashka, Ckamal35, Ckatz, Clicketyclack, ClockworkSoul, Closedmouth, Clueless1097, CoeurDeLion, Cohesion, CommonsDelinker, Computerjoe, Conversion script, Coolbho3000, CopperKettle, Corrigen, Courcelles, Craig Pemberton, Crazycomputers, Crisis, Csrfly D, Curtno-y08, Cyfal, DARTH SIDIOUS 2, DRTllbrg, DVdm, DabMachine, Danhauser, Darkzion102, Darth Panda, David Ashley, David D., DavidHackos, Dcelzinga, Deckiller, Dejudicibus, Delldot, Delta G, Demosthenes042, DerHexer, Derricky34, Devilkid2, Diannaa, Diberri, Dictyosome, Dijxtra, DirkvdM, Discospinster, Dj Capricorn, Doc glasgow, DocWatson42, Doctorx0079, Dogposter, DonScorgie, Donner60, Dota Gosu, DrMicro, DrSamba, DrSturm, DragonflySixtyseven, Dreadstar, Drmies, Drphilharmonic, Dtroestler, Duar9035, Durova, Dwmyers, Dysprosia, ESkog, Ec5618, Edgar181, Edward, Edward321, Ejrh, Eleassar, Elroch, Enz1, Epbr123, Erc, Erockrph, Esc12151, Eteq, Everyking, Evil saltine, Excirial, Extransit, Fabulous Creature, Fant, Faramir333, Featherfin, Fieldday-sunday, Finlay McWalter, Flewis, Flyguy649, Fraggle81, Freakofnurture, Fred Hsu, FreplySpang, Freshbakedpie, Frietjes, FuelWagon, FutureTrillionaire, GSMR, Gail, Gaius Cornelius, Gareth Griffith-Jones, Gene Nygaard, Geoking66, Giftlite, Gilderien, Gilliam, Glaisher, Glenn, Gogo Dodo, Gracenotes, Graham87, GrahamColm, Grammer & spelling stickler, Grantdesrosi, Grover cleveland, Gurch, Hadal, Hairy Dude, Hamiltondaniel, Harryboyles, Have fun with this, Hbent, Hdt83, Headbomb, HexaChord, Hi878, Hike395, Hodja Nasreddin, Hoffmeier, HorsePunchKid, Horseprerace, Husond, I AM THE GRINCH, ICanDrive55, IONTRANSP, IRP, Icarus, Icey, Illia Connell, ImmortalWombat, In Transit, Iohannes Animosus, Iridescent, IronGargoyle, Itemirus, Ixfd64, J.delanoy, J04n, J36miles, JForget, JFreeman, JWSchmidt, Jackfork, Jackol, Jagadish09, James086, JamesBWatson, Jamesx12345, Jan-hendrik15, Janko, Jbh2wiki, Jcao219, Jensbn, JerryFriedman, Jesse V., Jfdwolff, Jhbuk, Jim1138, JimR, Jiwhit01, Jlundell, Jmh649, Joel7687, John Price, John254, JohnThorne, Johner, Johnpseudo, Jojocurler, Jor, Jorfer, Josef kutryk, Josh Cherry, Josh Grosse, Jprg1966, Jrtayloriv, Jrugordon, Jsmith1234567890, Jugyhng, Julesd, Jumbuck, Jusdafax, KGasso, KING929, KSlayer, Kandar, Kanguole, KaterGator, Katieh5584, Kazvorpal, Kelvinsong, Kf4bdy, King of Hearts, Kingpin13, Knowledge Seeker, Kortoso, Koryant, Kristen Eriksen, Kubra, Kyle Barbour, L Kensington, LAX, La goutte de pluie, LadyofHats, Lagatapirata, Lawilkin, Lejean2000, Lensor, Lentower, Leuko, Lexivore, Lexor, LifeStar, LilHelpa, Lilac Soul, Lir, Lockeownzj00, Locomiguel, Logan, Loodog, Lord Anubis, Lordkazan, Louisemoves, Lrunge, Lulu.ucsd, Luna Santin, Luxot, M0rphzone, MONGO, Mabdul, Macdonald-ross, Machn, Madhero88, Magister Mathematicae, Magnus Manske, Makeemlighter, Malcolm Farmer, Malconfort, Malik Shabazz, Mani1, Marauder40, Marek69, MarieO, Marj Tiefert, Markhurd, Martial75, Masterall, Materialscientist, Matt Deres, Matthew138s, MatthewEHarbowy, Matthias M., Mattroxlol, Mav, Max Terry, MaxEspinho, Maxim Razin, McClamm, McDogm, McSly, Mccready, Mcrumiller, Meaghan, Metric, Mgiganteus1, MichaK, Michael C Price, Michael Crapo's DNA, Michael Devore, Michael Snow, Michaplot, Miguel Andrade, Mike2vil, Mini-Geek, Miracleworker5263, Miyagawa, Mkweise, Mojo Hand, Momo san, MonoAV, Morning277, Morten Scheibye-Knudsen, Mouse20080706, Mr Stephen, Mrscientistman, Mufka, MusikAnimal, Mx3, Mxn, Myanw, Mydogisbrown, Mygerardromance, Myspaceglue, Mythdon, N5iln, NBonawitz, NYHUG, Nagelfar, Narayanese, Nategraves, Nemesis of Reason, Nephron, NerdyScienceDude, NewEnglandYankee, Nezzadar, Niceguyedc, NickW557, Nicke L, Nnemo, NobelZong, Nonagonal Spider, Nono64, Noommos, Noosentaal, Nsk92, NuclearWarfare, NunoAgostinho, Nutster, Nwbeeson, Nyelvmark, OakRunner, Obli, Omegatron, OneMoreTime, Ooblahinfinite, Opabinia regalis, OrbitOne, Oubiwann, OwenX, PDH, PFHLai, Paine Ellsworth, Panda, Pandasthumb, Pauliekaboom, Paxsimius, Peak, Petpartisan, Phgao, Phidauex, Phil Boswell, Philip Trueman, Piano non troppo, Pigglesworth, Pikiwyn, Piltech, Pinethicket, Pinkadelica, Piolinfax, Plantsurfer, Pleather, Plumbago, PrestonH, Prokaryota, Proofreader77, Proxima Centauri, Psau, Pschemp, Pumpmeup, Purplelove121, Quentonamos, R. S. Shaw, RJHall, RW Marloe, RYNORT, Railfence, Rainbowwrasse, Ramitmahajan, RaseaC, Raymond Keller, Razorflame, Reach Out to the Truth, Reaper Eternal, RebekahThorn, Reconsider the static, RedWolf, Reinyday, RenamedUser01302013, Repku, Reywas92, Riana, Rich Farmbrough, Rizzardi, Rjwilmsi, Rmx256, Roadrunner, Rob Hooft, Robert M. Hunt, RobertStar20, Robinrocks, RodC, Romanm, Rory096, RoyBoy, Roybb95, Rrburke, Rror, Rsrikanth05, Rukifelth, Ruud Koot, RyanMcK, Ryanenglish, Ryrocker360, SD5, SIBERIANLUV, Sagaciousuk, Sam, Samsara, Sander123, Sathandi, Sbowers3, ScAvenger lv, Scientific29, Scohoust, Scrambles300, Scubasun, Sedmic, Seltar, Sfan00 IMG, Shadowjams, Shadowlynk, Sharu wikki, Shlomke, Sillybelle, Singhalawap, Sizzlebiscut, Sj, Slashme, Smack a ho, Smalljim, Smartse, Snow Blizzard, Sole Soul, Sowlos, Spamburgler, Sparge, Special-T, Spicemix, Spindrift, Springnuts, Squash, Squeakman, Squidonius, StAnselm, Steinsky, Stephenb, Stephenpratt, Storm Rider, SuperHamster, Supermanms, Swatjester, SwisterTwister, T-Fork, TJRC, Tameeria, Tarquin, TastyPoutine, Taw, Tbhotch, Teaktl17, Teardrop onthefire, Techdawg667, Techman224, TedPavlic, Tegiap, Teh nubkilr, Telecomsearch, Telfordbuck, TempAcctPubTerm, Template namespace initialisation script, TenOfAllTrades, Terminus Est 920, TerryE, Tetracube, Tgeairn, Thanatos666, Thanhluan001, The Rambling Man, The Thing That Should Not Be, The User 567, The wub, TheAMmollusc, TheDJ, TheKMan, Thingg, Think outside the box, Thomas Hopkins, Thunderboltz, Tide rolls, Tieddown, Tigershrike, Tim Q. Wells, TimVickers, Tocharianne, Tofutwitch11, Tolly4bolly, Tom Lougheed, Tomiko72, Tomm490, Tommy2010, Toniwikipendia, Traxs7, Triguy11, Trintith, Trusilver, Tuc72416, Tunzinette, Turkilas, TyA, Tycho, Ubiquitousnewt, Ugog Nizdast, Ultimate Star Wars Freak, Vanished user ikijeirw34iuaeolaseriffic, Vanished user uih38riiw4hjlsd, VashiDonsk, Vayne, Vergina11, Verrr55449988776655, Versus22, VeryVerily, Vikte, Vikus1234567890, Vinsfan368, WDavis1911, Waveclaira, Wavelength, Wayne Slam, Wayward, Where next Columbus?, Why Not A Duck, Widr, WikiLambo, Wikid77, Wikieditor06, WikipedianMarlith, WillowW, Winhunter, Wknight94, Woohookitty, Wowcody, Writ Keeper, WriterHound, Xestia, Xlaxplaya, Xris0, Yabti, Yaffley, Yamamoto Ichiro, Yunshui, Yuorme, Zafiroblue05, Zedshort, Zenibus, Zephyris, Zero sharp, Zocky, Zoicon5, Zzuuzz, Zzyzx11, , , , 1617 anonymous edits Vacuole Source: Contributors: (jarbarf), 090-chall,, 2D,, A More Perfect Onion, A3r0, AAA!, Acather96, Acekahn688, Addihockey10, Aditya, Aenioc, Aenoic, Ahoerstemeier, Aitias, Alan Liefting, Alansohn, Alex.muller, Alexius08, Alksub, Allens, Allstarecho, Alpha Quadrant (alt), Altruistic Egotist, Alxndr, AndyZ, Animum, ApostleJoe, Arbitrarily0, Arcadian, Areckers, Arnobarnard, Arthena, Avicennasis, Axeman89, Backpackadam, Bball4life15, Bensaccount, Biocysm, BlastOButter42, Bmicomp, Bob98133, Bobo192, Bomac, Boomshadow, Booyakz, Bradeos Graphon, Brim, Brion VIBBER, Bubbles215, Burner0718, Burnettgirl7, Calabe1992, Callanecc, Calor, Caltas, CambridgeBayWeather, Can't sleep, clown will eat me, CanadianLinuxUser, CardinalDan, Caroline.dahl atOxford, Chino, Chodorkovskiy, Chrisportelli, Christopher Parham, Christopher.hardy, Church of emacs, ClockworkSoul, ClockworkTroll, Closenplay, Clubingseals, Colorado, Conversion script, CopperKettle, CopyEditingGal, Courcelles, Cremepuff222, Crestkid100, Cyan, D, DARTH SIDIOUS 2, DO11.10, Dabomb87, Dadrepus, Daeroni, DanielCD, Dawn Bard, Dbfirs, DeadEyeArrow, DebateKid, Delirium, DeltaQuad, DerHexer, Desomnambulist, Dfrg.msc, Diannaa, Dictyosome, Dina, Discospinster, Djwarner, DoubleBlue, DougsTech, Doyley, Drmies, Dryman, Dwayne, EagleFan, Easchiff, Eleassar, Emo child312, Epbr123, Everyking, Evil saltine, Excirial, Explicit, Extransit, Falcon8765, Fan Railer, Faradayplank, Fbv65edel, Ferkelparade, FlyingToaster, Forluvoft, Frankenpuppy, Freddyd945, Freekman456, F, G3pro, Gail, George Rodney Maruri Game, George The Dragon, Gfoley4, Giftlite, Gilliam, Ginsuloft, Gogo Dodo, Gotyear, GraemeL, Graham87, Grim23, Grunt, Gurch, Gurchzilla, Guy M, Gkhan, Hadal, Hahahaha23, HalfShadow, Hennessey, Patrick, Heracles31, Heron, Hintss, Huggle, Hughcharlesparker, Hughitt1, Hut 8.5, Hw123456789, I am stuiped, II MusLiM HyBRiD II, IRP, IW.HG, Idarin, InShaneee, Ionutzmovie, Irishguy, J-stan, J.delanoy, JIP, JLaTondre, JNW, JaGa, Jamesx12345, Javert, Jay-Sebastos, Jaymark 13, Jeltz, Jimp, John254, Johnleemk, Johnslynch, Jojo122200, Jonathanfu, Josh Grosse, Juliancolton, Jusdafax, Jna runn, KC109, Kbh3rd, Keegscee, Keilana, Kelvinsong, Kendrick7, Killiondude, Kingcool228, KnowledgeOfSelf, Kraftlos, Kudret abi, L Kensington, La Pianista, Laceyc313, Latka, Law, LeaveSleaves, Lectonar, LedgendGamer, Lexor, LibLord, Lilac Soul, LizardJr8, Logan, Lord of Ruin, Lupo, MASQUERAID, MER-C, Maadal, Magister Mathematicae, Magnus Manske, Mani1, Marek69, Marshman, Martinp23, Materialscientist, Mattay83, Maxis ftw, Mcrumiller, Mejoribus, Mewasul, Michael Slone, Mike2vil, Mnolf, Moeron, Mojo Hand, Moogle10000, Morwen, Mr Adequate, Mulrich24, My Ubuntu, Mygerardromance, NAHID, NHRHS2010, NHSgrl22, Naat, Naqattaq, Narayanese, Nathan R. Noll, NawlinWiki, NeilN, NerdyScienceDude, NewEnglandYankee, Nihiltres, Nine Tail Fox, NinetyNineFennelSeeds, Nixn, Noah Salzman, Noctibus, Nonagonal Spider, NorwegianBlue, Nrets, Oldekop, OllieFury, Olorin28, Ongar the World-Weary, Optimale, Orbst, Oshwah, Oxymoron83, PFHLai, Palica, Paul Erik, Paul Klenk, Paxsimius, Persian Poet Gal, Pgk, Phantomsteve, Pharaoh of the Wizards, Philip Trueman, Pinethicket, Plantsurfer, Pollinator, Postglock, Proofreader77, Quintote, RFerreira, RadioFan, RattusMaximus, Raven in Orbit, Raywil, Razorflame, Rcsprinter123, Red Director, Redlentil, Res2216firestar, RickK, Rjd0060, Rjwilmsi, Ronhjones, Roybb95, Rrburke, Rror, Rspeer, Ryan032, Ryanro17, SJP, Sagaciousuk, ScAvenger lv, ScaldingHotSoup, Scapler, Scarian, Seaphoto, Sfmammamia, Shadowlynk, Sietse Snel, Sintaku, Sionus, Smartse, Soliloquial, Someguy1221, Sriharsh1234, Staxringold, Steinsky, Stephen Morley, Steve2011, Steven Zhang, Stismail, Svetko, Sylwia Ufnalska, SyntaxError55, THEN WHO WAS PHONE?, TYelliot, Tacoman1996, Tanthalas39, Tbhotch, Tcncv, Technopat, Template namespace initialisation script, Thatguyflint, The Arbiter, The Thing That Should Not Be, TheRanger, TheSchnitker, Theemathas, Thingg, Tiddly Tom, Tide rolls, TimVickers, Tolly4bolly, Tomgally, Tommy2010, Tomtom547, Traxs7, Trevor MacInnis, Trooney93, Trusilver, Tycho, Tyler, Tyrol5, Ugotstuffed, Ulcha, Ultimate Star Wars Freak, Una Smith, Unendingfear, Uusitunnus, VSquared, Vanished user 9i39j3, Vicki Rosenzweig, VolatileChemical, Vovkav, Vrenator, Vsion, WadeSimMiser, Wdgwdgwdg, Wellerd11, What!?Why?Who?, Wikipelli, Willybobbyjimbob, Wilson44691, Wingman13, Wizardman, Wlodzimierz, Wrathofjames, WriterHound, Wtmitchell, Yaris678, Yarnalgo, Yasuakinaito, Yintan, Yuanlongmaba, Zorahia, 1318 anonymous edits Lysosome Source: Contributors: 23th, 5 albert square, A8UDI, AJCham, Abce2, AbigailAbernathy, Adeez, AdjustShift, Adrian.benko, Akap007, Alansohn, Ale jrb, Allmightyduck, Altar, Amaury, Andrewpmk, Andrewrp, Anjana kelum, Ankush, Anna Lincoln, Apers0n, Aranea Mortem, Arcadian, Arjun01, Atethnekos, Athenacat3, Atif.t2, Axl, BD2412, Badmintonchampion, Bart133, Bassbonerocks, Belljaf, Bensaccount, Bentogoa, Bihco, Blechnic, Bluelightnight, Bobo192, Bogey97, Bookwormlady1100, Breawycker, BrokenSegue, Bryan Derksen, Btilm, CTZMSC3, Caltas, Cameron11598, Camw, Can't sleep, clown will eat me, CanadianLinuxUser, Cannawiki, Catgut, Cburnett, ChewySquirrel, Chhandama, Chickenfite, Chigejo, Cholmes75, ChrisGualtieri, Ciaccona, Cimorcus, Cirt, Cmichael, CommonsDelinker, Conversion script, Crazycomputers, Cs-wolves, Cue the Strings, Cuervolab, Cureden, CzarB, DARTH SIDIOUS 2, DAZM4N, DBigXray, DO11.10, Daniel5127, Davebridges, Dawn Bard, DeadEyeArrow, Deenoe, Delldot, Denisarona, Deor, DerHexer, Diberri, Dirjarmocksorz, Discospinster, Donner60, Drmies, Drphilharmonic, Dthibo, Duncan, Duncharris, Dwayne, Egil, Einhov, Ekotkie, Emily123654, Eminematt, Enchanter, Epbr123, Eric-Wester, Everyking, Excirial, Exzakin, FastLizard4, Femto, Fieldday-sunday, Fightinkilla, FlashingYoshi, Fluffernutter, Flyer22, Forever Dusk, Freiddie, Frogbucket, Giftiger wunsch, Giftlite, Gilliam, Ginsengbomb, Ginsuloft, Glane23, Glass Sword, GoShow, Gogo Dodo, Grim23, Gwib, Gwickwire, Haham hanuka, Hodja Nasreddin, I dream of horses, Iain99, Ikillwookies, Investneur, Ipodamos, Iridescent, Irina a, Isenkaje, Ixfd64, J.delanoy, JARSInc, JIP, JWSchmidt, Jackelfive, Jackol, Jackson Peebles, Jaimeglz, Jake Wartenberg, JamesAM, Jarble, Jeffrd10, Jenks, Jerry Zhang, Jfdwolff, Jhessian Zombie, Jim1138, JimVC3, John254, Jprg1966, Juliancolton, Jusdafax, Kaiwhakahaere, Kalaiarasy, Katieh5584, Kcox101, Kelvinsong, Kevin12xd, Khelmuth, Kinglz, KirbyRandolf, Kku, KnowledgeOfSelf, Kranix, Kristof vt, Kuru, Lagatapirata, Landon1980, LeaveSleaves, Lectonar, Lexor, Lightningprod123, LordVader1.0, LovesMacs, Lukehowell, Lystrablue, MER-C, Macy, Magicmazzie, Magioladitis, Mandarax, Mani1, Maniwar, Marek69, Mark Arsten, Martin451, Martpol, Materialscientist, Matijap, Mayarani500, Mayur, Mediran, MegaSpy, Mentifisto, Mgiganteus1, MichaK, Mike.lifeguard, Mikegrant, Mikewu610, Milkmanmike3121, Mintleaf, Miquonranger03, Miss Madeline, Moe Epsilon, MonoAV, MuZemike, Munita Prasad, Mwilso24, Mxn, MyNameIsNotBob, Mysdaao, Nagy, Nategraves, NawlinWiki, NellieBly, NewEnglandYankee, Nichwik, NinetyNineFennelSeeds, Nonagonal Spider, Nsaa, Nunh-huh, Oxymoron83, PFHLai, PM800, PaddyM, PatrciaR, Pats1, Paxsimius, Pepper, Peruvianllama, Pharaoh of the Wizards, PhilKnight, Philip Trueman, PiaNgoBucci, Piano non troppo, Pinethicket, PinkLinktoReality, Polluxian, Ppe42, Proud Muslim, Quaque, R500Mom, RUL3R, RadioFan, RainbowOfLight, Recycled.jack, RenamedUser01302013, Rettetast, Rich Farmbrough, Rickington, Ricky81682, Rocketboy50, Ronhjones, Rrburke, RyanGerbil10, RyanJones, STANE, Saimdawood, ScAvenger lv, Seaphoto, Sentausa, Sever, Shadowjams, Shlomke, Shoeofdeath, Shrimp wong, Shwimla, Sirtywell, Skarebo, Slightsmile, Slon02, Smartse, Snigbrook, Sodaplayer, Sophus Bie, Spangineer, Spi Waterwing, Spring Rubber, StaticGull, Steinsky, Stevegin3194, Steviewonder44, StokoSlap, Storm Rider, SubwayEater, Supercoop, Superyck, Swakeman, Sweikart, Syp, TOF1000, Tavilis, Taylorbio, Tdk327, TechnoFaye, Template namespace initialisation script, The Thing That Should Not Be, TheAMmollusc, TheRanger, Theda, Theone2be, Thingg, Tide rolls, Tim bates, TimVickers, Tom harrison, Tomtom547, Tschel,


Article Sources and Contributors

Tweichhart, TwizteDope, Tycho, Ubardak, UkPaolo, Useight, Vanished user uih38riiw4hjlsd, Velella, Vette92, W4chris, Warmonk, Wdflake, WhatamIdoing, White Shadows, Whoaz, Why Not A Duck, Widr, Wikipedian1234, Wikipelli, William Avery, Wimt, WingateChristopher, Wixom123, Wknight94, WriterHound, Wtmitchell, Wutsje, Wywin, Xcompton, Yamaguchi , Yamamoto Ichiro, Yarnalgo, Ykj4545, Youghurt, Zzuuzz, , 1181 anonymous edits Centrosome Source: Contributors: AdjustShift, Adrian.benko, Aleenf1, Alexei Kouprianov, Alperen, Anclation, Andre Engels, Arcadian, Avish2217, Bendzh, Blue Danube, Brainmachine, Brim, Calvin08, Cellbiology1, Ceyockey, Chichui, Chiefboz, ChrisDaniel58, Colababy, CommonsDelinker, Crystalcat55, D-Mob362, DBigXray, DMacks, DVdm, Dawn08, Dgw, Dougmerritt, Drbork, Duckyinc2, Empco, Epbr123, Epingchris, Eric Shalov, Faithlessthewonderboy, Faizan, Flying Canuck, Fotakos, Frietjes, Ggonnell, Hephaestos, Imilan, Instinctzz, Irestall, Iridescent, Irradiator, Itzrich5, JHunterJ, Jacyanda9, Jag123, Jcvamp, Jenks, Jumpingrat, Ka Faraq Gatri, Kelly Martin, Kelvinsong, Kinu, Kupirijo, La goutte de pluie, Lankenau, M1ss1ontomars2k4, Magioladitis, Manop, Merlintrix, MichaK, Minghong, Mortense, Mouce101, Munita Prasad, Narayanese, Naturespace, NightWolf1298, Ninawow, Nono64, Norm, Northamerica1000, OS2Warp, PFHLai, Pinethicket, Polypompholyx, Quintote, Qwaserdf25, Ratiocinate, Redfootedhurricane, Regidg, RenamedUser01302013, Rexodus, Rjwilmsi, RodC, Rogerburks, Seamstresserin, Sentriclecub, Serasuna, Shadowjams, SimonMayer, Siriuswhite1, Skunkboy74, Snowolfd4, Sowlos, Spjelgus, Squids and Chips, T@nn, Tabascoj, Tameeria, Thatguyflint, Thegreatgrabber, Touch Of Light, Twooars, Vanya Eccles, WAvegetarian, Wenli, Widr, WriterHound, , 175 anonymous edits DNA Source: Contributors: (, (jarbarf), 168.., 168..., 169, 17Drew, 1exec1, 2over0, 3dscience, 4u1e,, 7434be, 84user, 9FireStar, A D 13, A bit iffy, A-giau, AManWithNoPlan, Aaaxlp, Aatomic1, Academic Challenger, Acather96, Acer, Achowat, Adam Bishop, Adambiswanger1, Adamstevenson, Adashiel, Adenosine, Adrian.benko, Ahoerstemeier, Airconswitch, Aitias, Aj123456, Alai, Alan Au, Alarob, Alcides, Aldaron, Aldie, Alegoo92, Alexandremas, Alkivar, Alphachimp, Alzhaid, Amboo85, Anarchy on DNA, Ancheta Wis, Andonic, Andre Engels, Andrew wilson, Andreww, Andrij Kursetsky, AndroidOS, Andycjp, Anita1988, Anomalocaris, Antandrus, Ante Aikio, Anthere, Anthony, Anthony Appleyard, Antilived, Antony-22, Aquaplus, Aquilla34, ArazZeynili, Arcadian, Ardyn, Argionember, ArielGold, Armored Ear, Artichoker, Artoasis, Asbestos, Ashnard, Ashujo, Astronautics, Astrowob, Atlant, Aude, AustralianRupert, Autonova, Avala, Avicennasis, AxelBoldt, AySz88, AzaToth, B, BD2412, BMF81, BOK602, Banus, BaronLarf, Bbatsell, Bci2, Bcorr, Ben Webber, Ben-Zin, BenBildstein, Bender235, Benjah-bmm27, Bensaccount, Bernie Sanders' DNA, Bernstein0275, Bert Macklin, Bevo, Bhadani, Bhar100101, BiH, Bijee, BikA06, Bill Nelson's DNA, Billmcgn189, Biolinker, Biosthmors, Biriwilg, Bjwebb, Bkell, Blastwizard, Bloger, Blondtraillite, Bmtbomb, Bobblewik, Bobo192, Boghog, Bongwarrior, Borisblue, Bornhj, Brandmeister, Brian0918, Brighterorange, Briland, Brim, Brockett, Bruce1ee, BruceBlaus, Bryan, Bryan Derksen, Bubba73, CWY2190, Cacycle, Caerwine, Cainer91, Cal 1234, Calabe1992, Calaschysm, Can't sleep, clown will eat me, Canadaduane, Carbon-16, Carcharoth, Carlo.milanesi, Carlwev, Carstensen, Casliber, Cathalgarvey, CatherineMunro, CattleGirl, Causa sui, Cburnett, CephasE, Cerberus lord, Chaboura, Chanora, Chanting Fox, Chaojoker, Charm, Chenopodiaceous, Chick Bowen, Chill Pill Bill, Chino, Chodges, Chris 73, Chris84, ChrisGualtieri, Chuck Grassley's DNA, Chuck02, Cinnamon colbert, Clarkcj12, Clivedelmonte, Cloakedyoshi, ClockworkSoul, CloudNine, Coinmanj,, Colorajo, CommonsDelinker, Conversion script, Cool3, Coolawesome, Cor Ferrum, Coredesat, Cornacchia123, Cosmotron, Cradlelover123, Crazycomputers, Crowstar, Crusadeonilliteracy, CryptoDerk, Crzrussian, Csutric, Cubskrazy29, CupOBeans, Curehd, Curps, Cyan, Cyclonenim, Cyrius, D6, DARTH SIDIOUS 2, DIREKTOR, DJAX, DJRafe, DNA EDIT WAR, DNA is shyt, DVD R W, Daniel Olsen, Daniel987600, Danielkueh, Danny, Danny B-), Danski14, Darklilac, Darth Panda, Davegrupp, David D., David Eppstein, Davidartois, Davidbspalding, Dawn Bard, Daycd, Db099221, Dbabbitt, Dbfirs, Dbzhero5000, Dcirovic, Dcoetzee, DeAceShooter, DeadEyeArrow, Deflective, Delldot, Delta G, Deltabeignet, DevastatorIIC, Diberri, Dicklyon, Diego Grez, Diegomanzana, Digger3000, DigitalGhost, Digitalme, Dina, Djihinne1, Djm1279, Dlohcierekim's sock, Dmn, Dnacond, DocWatson42, Docjames, Doctor Faust, Docu, Dogposter, DonSiano, Donarreiskoffer, Dougweller, Dr d12, Dr.Kerr, DrKiernan, DrMicro, Dratman, Drbogdan, Drphilharmonic, Drpickem, Ds2207, Dudewheresmywallet, Dullhunk, Duncan.france, Dungodung, Dysmorodrepanis, E. Wayne, ERcheck, ESkog, Echo park00, Echuck215, EdJohnston, Eddycrai, Editing DNA, Edwy, Efbfweborg, Effeietsanders, Egil, ElTyrant, Elb2000, Eleassar777, EliasAlucard, ElinorD, Ellmist, Eloquence, Emoticon, Empty Buffer, Emw, Epingchris, Erik Zachte, ErrantX, Escape Artist Swyer, Esurnir, Etanol, Ettrig, EurekaLott, Everyking, Evil Monkey, Ewawer, Excirial, Execvator, FF2010, FOTEMEH, Fabhcn, Factual, Fagstein, Fastfission, Fconaway, Fcrick, Fences and windows, Fernando S. Aldado, Ffirehorse, Figma, Figure, Firetrap9254, Fishingpal99, Fjozk, Flavaflav1005, Florentino floro, Fnielsen, Forluvoft, Fox2k11, Freakofnurture, FreplySpang, Friendly Neighbour, Frostyservant, Fruge, Fs, Fvasconcellos, G3pro, GAThrawn22, GHe, GODhack, GVnayR, Gaara san, Gakrivas, Galoubet, Gary King, Gatortpk, Gazibara, GeeJo, Gene Nygaard, GeoMor, Giftiger wunsch, Giftlite, Gilisa, Gilliam, Gimmetrow, Gjuggler, Glen Hunt's DNA, Glenn, Gmaxwell, GoEThe, Goatasaur, Gogo Dodo, GoldRingChip, Golnazfotohabadi, GordonWatts, GorillaWarfare, Gracenotes, Graeme Bartlett, GraemeL, Grafikm fr, Graft, Graham87, GrahamColm, Grandegrandegrande, GregorB, Grover cleveland, Gurko, Gustav von Humpelschmumpel, Gutza, Gwsrinme, HJ Mitchell, Hadal, Hagerman, Hairchrm, Hairwheel, Hammersoft, Hannes Rst, Harianto, HayleyJohnson21, Hccc, Headbomb, Heathhunnicutt, Hephaestos, Heron, Hersfold, Hersfold tool account, Heyheyhack, Hgrosser, Hhhippo, Highfly3442, Hockey21dude, Hopefuldonor, Horatio, Hu, Hughdbrown, Hullaballoo Wolfowitz, Hurricanehink, Hut 8.5, Hvn0413, Hzh, I hate DNA, Ialsoagree, Iapetus, Icairns, Ilia Kr., Impamiizgraa, InShaneee, IncredibleWondersYes1, Infocidal, Inge-Lyubov, IronGargoyle, Isilanes, Isis07, Itub, Ixfd64, Iyentra Rasonica, Izehar, JForget, JHMM13, JSquish, JWBE, JWSchmidt, JWSurf, JZuehlke, Jacek Kendysz, Jack B108, Jackrm, JamesMLane, JamesMt1984, Janejellyroll, Jann, Jarhed, JasonK33, Javert, Jaxl, Jayron32, Jeka911, Jer ome, JeremyA, Jerzy, Jesse V., Jetsetpainter, Jh51681, Jiddisch, Jim1138, Jimriz, Jimwong, Jlh29, Jls043, Jmcc150, Jnorton7558, JoanneB, Joconnol, Jodon1971, Joeywallace9, Johanvs, John Mackenzie Burke, JohnArmagh, Johntex, Johnuniq, Jojit fb, JonMoulton, Jonrunles, Jonverve, Jorge Stolfi, Jorvik, JoshuaZ, Josq, Jossi, Jrtayloriv, Jstech, Jujutacular, Julian Diamond, Jumbo Snails, Junes, Juneythomas, Jwrosenzweig, Jynto, Kahlfin, Kapow, Karrmann, Katyare, Kaushlendratripathi, Kazkaskazkasako, Kbh3rd, Kbrose, Keegan, Keepweek, Keilana, Keiyashi, Kelly Martin, Kemyou, Kendrick7, KerryO77, Kevin B12, Kevmitch, Kghose, Khajidha, Khazar2, Kholdstare99, Kierano, King of Hearts, KingTT, Kingturtle, Kitch, Knowledge Seeker, KnowledgeOfSelf, Koavf, Kocio, KrakatoaKatie, Kums, Kungfuadam, Kuru, Kwamikagami, Kwekubo, L Kensington, LA2, LFaraone, La goutte de pluie, Lascorz, Latka, Lavateraguy, Laxative Brownies, Lee Daniel Crocker, Leevanjackson, Lemchesvej, Leptictidium, Lerdsuwa, Leuko, Lexor, Lfh, Lhenslee, Lia Todua, LightFlare, Lightmouse, Lightspeedchick, Ligulem, LikeLakers2, Lincher, Lion Wilson, Lir, Lklundin, Llongland, Llull, Lockesdonkey, Logical2u, Loginbuddy, Looxix, Loren36, Loris, Low-frequency internal, Luckas Blade, Luigi30, Luk, Lumos3, Luna Santin, Luuva, MER-C, MKoltnow, MONGO, MSGJ, Mac, Madeleine Price Ball, Madhero88, Magadan, Magioladitis, Magister Mathematicae, Magnus Manske, Mahmudmasri, Majorly, Malcolm rowe, Malo, Mandarax, Mandolinface, Mandyj61596, ManofQueens, Mantissa128, Marcus.aerlous, Marj Tiefert, Martin.Budden, MarvPaule, Mashin6, Master dingley, Materialscientist, Mattbr, Mattbrundage, Mattjblythe, Maurice Carbonaro, Mav, Max Baucus' DNA, Max Naylor, McDogm, Medessec, Medos2, Melaen, Melchoir, Mentalmaniac07, Mgiganteus1, Mgtoohey, Mhking, Michael Devore, Michael H 34, MichaelHa, Michaelas10, Michigan user, MidgleyDJ, Midnight Green, Midnightblueowl, Midoriko, Mika293, Mike Rosoft, Mikhail Ryazanov, Mikker, Mikko Paananen, Min.neel, Mindmatrix, Minimac, Mintman16, MisfitToys, Misza13, Mithent, Mjpieters, Mleefs7, Moink, Moorice, Mortene, Motley Crue Rocks, Mr Bungle, Mr Meow Meow, Mr Stephen, MrErku, Mshamza112, Mstislavl, Mstroeck, Mulad, Munita Prasad, Muro de Aguas, Mwanner, Mxn, Nakon, Nanettea, Nanodance, Narayanese, Natalie Erin, Natarajanganesan, Nate1028, NatureA16, Nauseam, Nbauman, Ne0Freedom, Neckro, Nemo bis, Netkinetic, Netoholic, Neutrality, Never give in, NewEnglandYankee, Niceguyedc, Nick Number, Nighthawk380, NighthawkJ, Nihiltres, Nirajrm, Nishkid64, Nitecrawler, Nitramrekcap, No Guru, NoIdeaNick, NochnoiDozor, Nofatlandshark, Nohat, Nono64, Northfox, NorwegianBlue, Nthornberry, NuclearWarfare, Nunh-huh, O.Koslowski, OBloodyHell, OOODDD, Obli, Oblivious, Ocaasi, Ocolon, OekelWm, Ojl, Oliverrichardson, Omicronpersei8, Onco p53, Opabinia regalis, Opelio, Orphan Wiki, Orrin Hatch's DNA, Orthologist, Ortolan88, Otterinfo, Ouishoebean, Outriggr, OwenX, P99am, PDH, PFHLai, PaePae, Paine Ellsworth, Pakaran, Pascal666, Patrick0Moran, Patrick2480, Patstuart, Paul Foxworthy, Paul venter, PaulGS, Paulinho28, Pcb21, Pde, Peak, Pediaknowledge, Pedro, Perseus, Son of Zeus, Persian Poet Gal, Peter Isotalo, Peter K., Peter Winnberg, Pgan002, Phil2793, Philip Trueman, PhilipO, Phoenix Hacker, Pierceno, PierreAbbat, Pifactorial, Pigman, Pigmietheclub, Pilotguy, Pinethicket, Pkank, Pkirlin, Poor Yorick, Portugue6927, Potatoswatter, Prathfig, Preston47, Prestonmag, Priscilla 95925, Pristontale111, Pro crast in a tor, ProDawg5, Prodego, Psora, PsyMar, Psymier, Puffin, Pumpkingrower05, Pyrospirit, Quebec99, Quickbeam, Qutezuce, Qxz, R'n'B, R. S. Shaw, RDBrown, RJC, RJaguar3, RK, RSido, Ragesoss, Rajwiki123, RandomLittleHelper, RandomP, Randomblue, Raul654, Raven in Orbit, Ravidreams, Rdb, Rdsmith4, Red Director, Reddi, Rednblu, Redneckjimmy, Redquark, Retired username, Rettetast, RexNL, Rezecib, Rich Farmbrough, RichG, Richard Durbin's DNA, Ricky81682, Rishi.bedi, Rjwilmsi, Roadnottaken, Robdurbar, RobertG, Rocastelo, RoddyYoung, Rohitsuratekar, Rory096, Rotem Dan, Roy Brumback, RoyBoy, RoyLaurie, Royalguard11, Rr2wiki, RunOrDie, Russ47025, RxS, RyanGerbil10, Ryulong, S77914767, SCEhardt, STAN SWANSON, SWAdair, Sabbre, Safwan40, Sakkura, Salix alba, SallyForth123, Sam Burne James, Samsara, Samuel, Samuel Blanning, SandyGeorgia, Sangak, Sango123, Sangwine, Savidan, Saxophilist, Scarce, Sceptre, Schapel, Schutz, Sciencechick, Scientific29, Scincesociety, Sciurin, Scope creep, Scoterican, Sean William, SeanMack, Seans Potato Business, Seb az86556, SebastianHawes, Seldon1, SemperBlotto, Sentausa, Serephine, Sgt. R.K. Blue, Shadowlynk, Shanes, ShaunL, Shekharsuman, Shizhao, Shmee47, Shoy, SimonD, Simultaneous, Sintaku, Sir.Loin, Sjjupadhyay, Sjollema, Sloth monkey, Slrubenstein, Sly G, SmilesALot, Smithbrenon, Snow Blizzard, Snowmanradio, Snowolf, Solipsist, Someone else, Somoza, Sonett72, Sopoforic, Spathaky, Spaully, Spectrogram, Spiff, Splette, Spondoolicks, Spongebobsqpants, SpuriousQ, Squidonius, Squirepants101, Statsone, Steel, Steinsky, Stemonitis, Stephenb, Steve Quinn, SteveHopson, Stevertigo, Stevietheman, Stewartadcock, Stigmatella aurantiaca, Stuart7m, Studerby, Stuhacking, SupaStarGirl, Supreme Deliciousness, Supspirit, Susvolans, Sverdrup, Swid, Switchercat, THFC1996, Taco325i, Takometer, TakuyaMurata, Tariqabjotu, Tarret, Taulant23, Tavilis, Tazmaniacs, Tbhotch, Tdadamemd, Ted Longstaffe, TeleComNasSprVen, Tellyaddict, TenOfAllTrades, Terraguy, Test100000, TestPilot, The Man in Question, The Rambling Man, The WikiWhippet, TheAlphaWolf, TheChrisD, TheKMan, TheRanger, Theodolite, Theopolisme, Thine Antique Pen, ThoHug, Thorwald, ThreeDaysGraceFan101, Thue, Tiddly Tom, Tide rolls, TigerShark, TimVickers, Timewatcher, Timir2, Timl, Timrollpickering, Timwi, Tmueck, Tobogganoggin, Toby Bartels, TobyWilson1992, Tom Allen, Tom Harkin's DNA, Tom.Reding, Tomgally, Toninu, Tony1, Tonyrenploki, Torchiest, Toto Azro, Tpbradbury, Travelbird, Trd300gt, Treisijs, Trent Lott's DNA, Triwbe, Troels Arvin, Trusilver, Tryptofish, Tstrobaugh, Tufflaw, TuringMachine17, Turnstep, Twilight Realm, Ty146Ty146, UBeR, Ucucha, Uluru345, Unconventional, Unint, Unukorno, Usergreatpower, Username 772, Utcursch, Ute in DC, Uthbrian, Vaernnond, Vandelizer, Vanished user, Vanished user 19794758563875, Vary, Virtualphtn, Visium, Vividonset, VladimirKorablin, Vogel2014, Vsmith, Vyasa, WAS 4.250, WAvegetarian, WHeimbigner, WJBscribe, Wafulz, WarthogDemon, Wavelength, Webclient101, WelshMatt, West Brom 4ever, WhatamIdoing, Where, Whosasking, Whoutz, Why My Fleece?, Wik, Wiki alf, Wiki emma johnson, Wikiborg, Wikipedia Administration, Will Beback Auto, William Pietri, WillowW, Wimt, Wizardist, Wkboonec, Wknight94, Wmahan, Wnt, Wobble, WolfmanSF, Woodsrock, Woohookitty, Wouterstomp, Wwwwolf, YOUR DNA, Yahel Guhan, Yamamoto Ichiro, Yamla, YanWong, Yansa, Yaser al-Nabriss, Yasha, Yikrazuul, Yobol, Yomama9753, Youngdro2, Younusporteous, Yurik, ZScout370, Zahid Abdassabur, Zahiri, Zanaq, Zarex, Zazou, Zell Miller's DNA, Zephyris, Zoicon5, Zouavman Le Zouave, Zsinj, Zven, Zynwyx, 1468 anonymous edits Genome Source: Contributors:, 168..., A.amitkumar, A.bit, A.cristianlucian, Acroterion, AdamRetchless, Adamace90, Adenosine, Adrian.benko, Agathman, Ahoerstemeier, Aircorn, Alansohn, Alex.muller, Alexbateman, Alglascock, AlistairMcMillan, Allstarecho, Altairisfar, Amigoswiki, Amorymeltzer, AnneDELS, Arthena, Askpat13, Awesome girl09, AxelBoldt, Axelv, Azcolvin429, Banus, Ben-Zin, Betawarrior60, Betterusername, Black Kite, Bomac, Bradleysp1, Brona, Bryan Derksen, CHJL, Calebe, Californiadreams, Camera-PR, CanadianLinuxUser, Candelario Hanson, CanisRufus, Carptesticle,, Centrx, Cephal-odd, Ceyockey, Chaos, ChazYork, Chino, ClockworkSoul, Cntras, Commutator, Conversion script, CsDix, Cyborg1981, Cyclopia, DMacks, DVD R W, Danjel, Dave Blank, Dejvid, DelianDiver, Delta G, Derek Andrews, Discospinster, Dmb000006, Dnaphd, Doctor Faust, DoctorDNA, Dogposter, Doucher, Dr. ambitious, Drinkybird, Drmies, Emw, EoD, Equinexus, Eric Kvaalen, Estevezj, Evolver, Fama Clamosa, Felipe


Article Sources and Contributors

Sobreira Abraho, Ferengi, FerzenR, Firsfron, Fish and karate, Flavonoid, For7thGen, Forluvoft, Frap, Fuzheado, GSlicer, Genome biologist KS, Genometer, Geoff, George Church, George Gastin, Giftlite, Gilliam, Gitana127, Glenn, Gogo Dodo, Grmagne, Gsp, Gulmammad, Haeinous, HangingCurve, Hawkeye356, Haywardlc, Herbee, Heron, Hgamboa, Holycow32989, Hubcap21, Huttarl, Immunize, Indianpjn, Insanity Incarnate, InternetMeme, Ioverka, Iridescent, IstvanWolf, Iwilcox, JH-man, Jaums, Jbkgiants, Jenks, Jesse V., Jim1138, Jo3sampl, Joconnol, John Mackenzie Burke, Johntex, Johnuniq, JongPark, Jonverve, Joshafina, Julesd, KGasso, Kaarel, Kafziel, Kaiwen1, Karlthegreat, Katieh5584, Kbradnam, Kducey, Keilana, Kylic, LC, Lambiam, Larryisgood, Laurinavicius, Lavateraguy, Lbeaumont, Lexor, Lightmouse, Llull, Loren36, Lova Falk, Madeleine Price Ball, Magnus Manske, Manchester123456789, Marian, MarionADelgado, Marj Tiefert, Mark R Johnson, MartinPoulter, MartinezMD, Matt.whitby, Matt11111111, Miciah, Mikael Hggstrm, Mindmatrix, Mindspillage, Minimice, Mkh388, Mogism, Moink, Moorelin, Moreschi, MrPMonday, MusikAnimal, Mxn, Namazu-tron, NawlinWiki, Netrapt, Nick Thompson, Niteowlneils, No Guru, Nono64, Northamerica1000, NotWith, Ohnoitsjamie, Onceonthisisland, Onco p53, Oneiros, Ontarioboy, Open2universe, Orange Suede Sofa, Ottava Rima, Oxwil, PDH, PSimeon, Paranthaman, Pathh, Patho, Paul Abrahams, Peteruetz, Pewwer42, Pgan002, Pifactorial, Polyhedron, PradeepArya1109, Purnajitphukon, PuzzletChung, Pvosta, Quadell, Quintote, RJASE1, Raccoon Fox, Ramujana, Randomaperry, Realfoxxx, Reinyday, Rhetth, Rich Farmbrough, Rich.lewis, Rjwilmsi, Rkitko, Ronz, Rosieredfield, SEWilco, Sabedon, Sabisteb, Sampsonjk, Samsara, Savant1984, ScAvenger lv, Scarian, Schutz, Scilit, Scwlong, SeanMack, Seglea, Sentausa, Several Times, Shinkolobwe, Shoefly, Shogatetus, Shrimp wong, Silvrous, Sjjupadhyay, Skier Dude, Sluzzelin, Smalljim, Smartse, Snek01, SocialContext, Specs112, SpuriousQ, Steinsky, Stephen Turner, SteveChervitzTrutane, Stevertigo, Stroppolo, Stwalkerster, Summer Song, Sumukal, Svetovid, Tareqiu, Taxman, The Rationalist, The Storm Surfer, TheAMmollusc, TheAlphaWolf, Thecheesykid, Thorwald, TimVickers, Tomaschwutz, Tomyhoi, Tosendo, Tpbradbury, TrenSur, True Pagan Warrior, Trusilver, Turnstep, Two hundred hum, Vanderesch, Vasi31, Veryhuman, Vipinhari, Vrenator, Vsmith, WadeSimMiser, Waerfeles, Wavelength, Wenfuli, Wet dog fur, Whosasking, Wikiborg, Will Beback Auto, Woodsrock, Woohookitty, Wootini, Xmteam, YaguchiA, Youandme, Youssefa, Youssefsan, Zakarps, Zashaw, ZeWrestler, Zfr, Zundark, , 349 anonymous edits


Image Sources, Licenses and Contributors


Image Sources, Licenses and Contributors

File:Wilson1900Fig2.jpg Source: License: Public Domain Contributors: Edmund Beecher Wilson File:celltypes.svg Source: License: Public Domain Contributors: Science Primer (National Center for Biotechnology Information). Vectorized by Mortadelo2005. Image:Average prokaryote cell- en.svg Source: License: Public Domain Contributors: Mariana Ruiz Villarreal, LadyofHats Image:Animal cell structure en.svg Source: License: Public Domain Contributors: LadyofHats (Mariana Ruiz) Image:Plant cell structure svg.svg Source: License: Public Domain Contributors: LadyofHats (Mariana Ruiz) File:Blausen 0208 CellAnatomy.png Source: License: Creative Commons Attribution 3.0 Contributors: User:BruceBlaus File:DAPIMitoTrackerRedAlexaFluor488BPAE.jpg Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: IP69.226.103.13 Image:Endomembrane system diagram no text nucleus.png Source: License: Public domain Contributors: Peter Znamenskiy at en.wikipedia Image:Three cell growth types.png Source: License: GNU Free Documentation License Contributors: User:Bevo, User:JWSchmidt Image:Proteinsynthesis.png Source: License: Public Domain Contributors: Incnis Mrsi, Laikayiu, Torsch, 1 anonymous edits File:Stromatolites.jpg Source: License: Public Domain Contributors: P. Carrara, NPS File:PD-icon.svg Source: License: Public Domain Contributors: Alex.muller, Anomie, Anonymous Dissident, CBM, MBisanz, PBS, Quadell, Rocket000, Strangerer, Timotheus Canens, 1 anonymous edits Image:Cell membrane detailed diagram 4.svg Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: derivative work: Dhatfield (talk) Cell_membrane_detailed_diagram_3.svg: *derivative work: Dhatfield (talk) Cell_membrane_detailed_diagram.svg: LadyofHats Mariana Ruiz File:Cell membrane detailed diagram en.svg Source: License: Public Domain Contributors: LadyofHats Mariana Ruiz File:Blausen 0213 CellularDiffusion.png Source: License: Creative Commons Attribution 3.0 Contributors: User:BruceBlaus Image:Fluid Mosaic.svg Source: License: Creative Commons Attribution-ShareAlike 3.0 Unported Contributors: Jerome Walker Image:Alpha Intercalated Cell Cartoon.svg Source: License: Creative Commons Attribution 3.0 Contributors: Rswarbrick Image:Membrane lipids.png Source: License: Public Domain Contributors: Cwbm (commons), Dcirovic Image:Crowded cytosol.png Source: License: Public Domain Contributors: TimVickers File:Animal Cell.svg Source: License: Creative Commons Zero Contributors: User:Kelvinsong Image:Carboxysome.png Source: License: Creative Commons Attribution 3.0 Contributors: T. Yeates, M. Yeager and K. Dryden Image:Localisations02eng.jpg Source: License: Creative Commons Attribution-Sharealike 2.5 Contributors: Jeremy Simpson and Rainer Pepperkok File:Carboxysomes EM.jpg Source: License: Creative Commons Attribution 3.0 Contributors: Tsai Y, Sawaya MR, Cannon GC, Cai F, Williams EB, Heinhorst S, Kerfeld CA, Yeates TO File:Leeuwenhoek1719RedBloodCells.jpg Source: License: Public Domain Contributors: Antoni van Leeuwenhoek Image:Flemming1882Tafel1Fig14.jpg Source: License: Public Domain Contributors: Walther Flemming. Professor der Anatomie in Kiel. Image:Diagram human cell nucleus.svg Source: License: Public Domain Contributors: Mariana Ruiz LadyofHats Image:NuclearPore crop.svg Source: License: Creative Commons Attribution-Sharealike 2.5 Contributors: User:Adenosine, User:LadyofHats Image:MouseChromosomeTerritoriesBMC Cell Biol6-44Fig2e.jpg Source: License: Creative Commons Attribution 2.0 Contributors: Robert Mayer, Alessandro Brero, Johann von Hase, Timm Schroeder, Thomas Cremer, Steffen Dietzel Image:Micrograph of a cell nucleus.png Source: License: Public Domain Contributors: User:Opabinia regalis, User:PNG crusade bot, User:Remember the dot File:Blausen 0212 CellNucleus.png Source: License: Creative Commons Attribution 3.0 Contributors: User:BruceBlaus File:Transcription label en.jpg Source: License: GNU Free Documentation License Contributors: InfoCan, Jacopo Werther, TimVickers, 1 anonymous edits Image:RanGTPcycle.png Source: License: unknown Contributors: Shao at uk.wikipedia File:Mitosis-fluorescent.jpg Source: License: Public domain Contributors: Deadstar, Glenn, Hikke, Iori951, Kam Solusar, Lin1, Monkeybait, Mortadelo2005, Opabinia regalis, Pieter Kuiper, Sanbec, Steveprutz, Trelio, 10 anonymous edits Image:redbloodcells.jpg Source: License: Public domain Contributors: Dietzel65, Habj, Ranveig, Shizhao, Simon Shek, Solon, Sundar, Thuresson Image:Chr2 orang human.jpg Source: License: Creative Commons Attribution-Sharealike 2.5 Contributors: Verena Schubel, Stefan Mller, Department Biologie der Ludwig-Maximilians-Universitt Mnchen. Image:MouseChromosomeTerritoriesBMC Cell Biol6-44Fig2.jpg Source: License: Creative Commons Attribution 2.0 Contributors: Robert Mayer, Alessandro Brero, Johann von Hase, Timm Schroeder, Thomas Cremer, Steffen Dietzel Image:PLoSBiol3.5.Fig1bNucleus46Chromosomes.jpg Source: License: Creative Commons Attribution 2.5 Contributors: Andreas Bolzer, Gregor Kreth, Irina Solovei, Daniela Koehler, Kaan Saracoglu, Christine Fauth, Stefan Mller, Roland Eils, Christoph Cremer, Michael R. Speicher, Thomas Cremer Image:Nucleus&Nucleolus.gif Source: License: Public Domain Contributors: Daniel Mietchen, Hoffmeier, Ies, Kurgus File:Peptide syn.png Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: Boumphreyfr Image:ribosome shape.png Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: Vossman Image:10 small subunit.gif Source: License: Public Domain Contributors: Animation by David S. Goodsell, RCSB Protein Data Bank Original uploader was TimVickers at en.wikipedia Image:10 large subunit.gif Source: License: Public Domain Contributors: Animation by David S. Goodsell, RCSB Protein Data Bank Original uploader was TimVickers at en.wikipedia

Image Sources, Licenses and Contributors

File:Ribosomer i arbete.png Source: License: GNU Free Documentation License Contributors: GeorgHH, Maksim, Qef Image:Liposome scheme-en.svg Source: License: Creative Commons Attribution-Sharealike 3.0,2.5,2.0,1.0 Contributors: SuperManu File:Sarfus.LipidVesicles.jpg Source: License: Public Domain Contributors: Nanolane Image:Hemozoin in food vacuole.jpg Source: License: Creative Commons Attribution 3.0 Contributors: Jani D, Nagarkatti R, Beatty W, Angel R, Slebodnick C, Andersen J, Kumar S, Rathore D. Image:Clara cell lung - TEM.jpg Source: License: Public Domain Contributors: Louisa Howard Image:nucleus ER golgi.svg Source: License: Creative Commons Attribution 3.0 Contributors: Nucleus ER golgi.jpg: Magnus Manske Derivative work: Pbroks13 (talk) File:Blausen 0350 EndoplasmicReticulum.png Source: License: Creative Commons Attribution 3.0 Contributors: User:BruceBlaus Image:Human leukocyte, showing golgi - TEM.jpg Source:,_showing_golgi_-_TEM.jpg License: Public Domain Contributors: Louisa Howard File:Golgi apparatus (borderless version)-en.svg Source: License: Creative Commons Attribution 3.0 Contributors: User:Kelvinsong File:Blausen 0435 GolgiApparatus.png Source: License: Creative Commons Attribution 3.0 Contributors: User:BruceBlaus Image:Nucleus ER golgi.svg Source: License: Creative Commons Attribution 3.0 Contributors: Nucleus ER golgi.jpg: Magnus Manske Derivative work: Pbroks13 (talk) Image:FluorescentCells.jpg Source: License: Public Domain Contributors: Amada44, DO11.10, Daniel Mietchen, Emijrp, Hannes Rst, Leyo, Liaocyed, NEON ja, Origamiemensch, Sentausa, Splette, Timur lenk, Tolanor, Trelio, 10 anonymous edits Image:MEF microfilaments.jpg Source: License: Creative Commons Attribution-ShareAlike 3.0 Unported Contributors: Y tambe Image:KeratinF9.png Source: License: GNU Free Documentation License Contributors: Dietzel65, Jonik, Maksim, 1 anonymous edits Image:Btub.jpg Source: License: GNU Free Documentation License Contributors: Original uploader was Jeffrey81 at nl.wikipedia File:Mitochondria, mammalian lung - TEM.jpg Source:,_mammalian_lung_-_TEM.jpg License: Public Domain Contributors: Louisa Howard File:Mitochondrion mini.svg Source: License: Creative Commons Zero Contributors: User:Kelvinsong File:Blausen 0644 Mitochondria.png Source: License: Creative Commons Attribution 3.0 Contributors: User:BruceBlaus File:MitochondrionCAM.jpg Source: License: Public domain Contributors: Original uploader was Carmmann (talk) at en.wikipedia. Later version(s) were uploaded by Pschemp at en.wikipedia. File:ERMES.png Source: License: Creative Commons Zero Contributors: Apeckwiki File:Electron transport chain.svg Source: License: Public Domain Contributors: User:T-Fork File:Chondrocyte- calcium stain.jpg Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: Robert M. Hunt File:Mitochondrial DNA en.svg Source: License: GNU Free Documentation License Contributors: derivative work: Shanel (talk) Mitochondrial_DNA_de.svg: translation by Knopfkind; layout by jhc File:Plant cell structure svg vacuole.svg Source: License: Public Domain Contributors: Mariana Ruiz LadyofHats, labels by Dake modified by smartse File:Biological cell vacuole.svg Source: License: GNU Free Documentation License Contributors: MesserWoland and Szczepan1990 modified by smartse File:Rhoeo Discolor - Plasmolysis.jpg Source: License: Creative Commons Attribution-Sharealike 2.0 Contributors: Mnolf File:Centrosome (borderless version)-en.svg Source: License: Creative Commons Attribution 3.0 Contributors: User:Kelvinsong Image:Molly Sheehan Wikipedia 1.jpg Source: License: Public Domain Contributors: Original uploader was Redfootedhurricane at en.wikipedia Image:Cytokinesis-electron-micrograph.jpg Source: License: Public Domain Contributors: Grafite, Rasbak, TommyBee, Was a bee, Zephyris File:DNA NoBB.png Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: Zephyris File:ADN animation.gif Source: License: Public Domain Contributors: brian0918 File:DNA chemical structure.svg Source: License: Creative Commons Attribution-ShareAlike 3.0 Unported Contributors: User:Madprime File:DNA orbit animated static thumb.png Source: License: GNU Free Documentation License Contributors: 84user adapting file originally uploaded by Richard Wheeler (Zephyris) at en.wikipedia File:DNA-ligand-by-Abalone.png Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: P99am File:Base pair GC.svg Source: License: Public Domain Contributors: Yikrazuul File:Base pair AT.svg Source: License: Public Domain Contributors: Yikrazuul File:A-DNA, B-DNA and Z-DNA.png Source:,_B-DNA_and_Z-DNA.png License: GNU Free Documentation License Contributors: Original uploader was Richard Wheeler (Zephyris) at en.wikipedia File:Parallel telomere quadruple.png Source: License: GNU Free Documentation License Contributors: Thomas Splettstoesser ( File:Branch-dna-single.svg Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: Otterinfo, Sarang, 1 anonymous edits File:Branch-DNA-multiple.svg Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: Otterinfo, Sarang File:Cytosin.svg Source: License: Public Domain Contributors: NEUROtiker File:5-Methylcytosine.svg Source: License: Public Domain Contributors: Yikrazuul (talk) File:Thymin.svg Source: License: Public Domain Contributors: NEUROtiker File:Benzopyrene DNA adduct 1JDG.png Source: License: GNU Free Documentation License Contributors: Benjah-bmm27, Bstlee, 1 anonymous edits File:T7 RNA polymerase.jpg Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: User:Splette


Image Sources, Licenses and Contributors

File:DNA replication en.svg Source: License: Public Domain Contributors: LadyofHats Mariana Ruiz Image:Nucleosome1.png Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: User:Splette File:Lambda repressor 1LMB.png Source: License: GNU Free Documentation License Contributors: Original uploader was Zephyris at en.wikipedia File:EcoRV 1RVA.png Source: License: GNU Free Documentation License Contributors: Original uploader was Zephyris at en.wikipedia File:Holliday Junction.svg Source: License: Public Domain Contributors: derivative work: File:Holliday junction coloured.png Source: License: GNU Free Documentation License Contributors: Original uploader was Zephyris at en.wikipedia File:Chromosomal Recombination.svg Source: License: Creative Commons Attribution 2.5 Contributors: David Eccles (Gringer) File:DNA nanostructures.png Source: License: Creative Commons Attribution 2.5 Contributors: (Images were kindly provided by Thomas H. LaBean and Hao Yan.) File:Maclyn McCarty with Francis Crick and James D Watson - 10.1371 journal.pbio.0030341.g001-O.jpg Source: License: Creative Commons Attribution 2.5 Contributors: Marjorie McCarty File:Symbol template class.svg Source: License: Public Domain Contributors: Anomie File:NHGRI human male karyotype.png Source: License: Public Domain Contributors: Courtesy: National Human Genome Research Institute File:Genome size vs number of genes.svg Source: License: Creative Commons Attribution-Sharealike 3.0 Contributors: User:Estevezj




Creative Commons Attribution-Share Alike 3.0 //