Organelle/ Inclusion Functions
Nucleus Storage and use of genome
Nucleolus Synthesis of rRNA and
partial assembly of
ribosomal subunits
Involved in regulation of cell
cycle
Plasma membrane Ion and nutrient transport 
 Not visible


Recognition of
environmental signal
 cell; two inner and outer


Cell-to-cell and cell-to-
extracellular matrix
adhesions
rER Binds ribosomes engaged
in translating mRNA for
proteins
destined for secretion or for
membrane insertion
Chemical modifications of
proteins and membrane
lipid synthesis
sER Lipid and steroid
metabolism
Golgi apparatus Chemical modification of
proteins


Sorting and packaging of
molecules for secretion or
transport to other
organelles
Maintenance and renewal
of cell membrane
Secretory vesicles Transport and storage of
secreted proteins to plasma
membrane
Mitochondria Aerobic energy supply
(oxidative phosphorylation,
ATP)
Endosomes Transport of endocytosed
material


Biogenesis of lysosomes
LM features
Largest organelle within the
cell with distinct boundary


Often visible nucleoli and
chromatin pattern regions
Roughly circular,
basophilic region within
the nucleus


Visible in living cells
throughout interphase with
interference microscopy
Basophilic region of
cytoplasm
referred to as
ergastoplasm
Not visible


Cytoplasm in region of
sER may exhibit distinct
eosinophilia
Sometimes observed as
“negative staining” region


Appears as network in
heavy metal–stained
preparations
Visible in living cells with
interference microscopy
Observed only when
vesicles are very large
Sometimes observed in
favorable situations (e.g.,
liver or nerve cells) as
miniscule, dark dots; visible
in living cells stained with
vital dyes (e.g., Janus
green)
Not visible
EM features Associated Diseases
Surrounded by two Inherited genetic diseases;
membranes (nuclear environmentally
envelope) containing induced mutations
nuclear pore complexes
and perinuclear cisternal
space
Regions with condensed
and diffused chromatin
pattern (heterochromatin
and euchromatin)
Dense, nonmembranous Werner syndrome
structure containing fibrillar (premature aging disease)
and granular material
Malfunctions of cell cycle
leading to cancerogenesis
External membrane and Cystic fibrosis (ABC
membranes surrounding transporter)

membranous organelles of 

Intestinal malabsorption
electron-dense layers syndromes

separated by 

intermediate electron-lucent Lactose intolerance
layer
Flattened sheets, sacs, and Pseudoachondroplasia
tubes of membranes with 

attached ribosomes Calcium phosphate
dihydrate crystal deposition
disease
Flattened sheets, sacs, and Hepatic endoplasmic
tubes of membranes reticular storage disease
without attached ribosomes
Stack of flattened I-cell disease
membrane sheets, often 

adjacent to one side of Polycystic kidney disease
nucleus
Many relatively small, Lewy bodies of Parkinson’s
membrane-bounded disease
vesicles of uniform 

diameter, often polarized Proinsulin diabetes
on one side of cell
Two-membrane system: Mitochondrial myopathies
outer membrane and inner such as MERRFa,
membrane arranged in MELASb, Kearns-Sayre
numerous folds (cristae) syndromes, and

 Leber’s hereditary optic
In steroid-producing cells, atrophy
inner membrane arranged
in tubular cristae
Tubulovesicular structures M-6-P receptor deficiency
with subdivided lumen
containing electron-lucent
material or
other smaller vesicles
 Lysosomes Digestion of
macromolecules
Peroxisomes Oxidative digestion
Cytoskeletal elements Various functions, including
cell motility, cell
adhesions, intracellular and
extracellular transport
Maintenance of cellular
skeleton
Ribosomes Synthesis of protein by
translating protein-coding
sequence from mRNA
Proteasomes Degradation of
unnecessary and damaged
proteins that are labeled for
destruction with ubiquitin
Glycogen Short-term storage of
glucose in the form of
branched polymer
 
 like inclusions
Found in liver, skeletal
muscle, and adipose tissue
Lipid droplets Storage of esterified forms
of fatty acids as high
energy
storage molecules
LSDs
1. Disorders of sphingolipid degradation
2. Disorders of glycoprotein degradation
3. Disorders of glycosaminoglycan degradation
!
Visible only after special
enzyme histochemical
staining
Visible only after special
enzyme histochemical
staining
Only observed when
organized into large
structures
(e.g., muscle fi brils)
Not visible
Not visible
Observed as a “purple
haze” region of cytoplasm 
 extremely dense grape-
metachromasia with
toluidine blue–stained
specimen
Readily visible when
extremely large (e.g., in
adipocytes)


Appear as large empty
holes in section (lipid itself
is
usually removed by
embedding solvents)
Membrane-bounded
vesicles, often electron
dense
Membrane-bounded
vesicles, often with
electron-dense crystalloid
inclusions
Long, linear staining pattern
with width and features
characteristic of each
filament type
Minute dark dots, often
associated with the rER
Difficult to distinguish from
other matrix proteins
Nonmembranous,
Nonmembranous inclusions


Generally appear as a void
in the section
LSDs
Zellweger’s syndrome
Immotile cilia syndrome,
Alzheimer’s disease,
epidermolysis bullosa
Ribosomal dysfunction in
Alzheimer’s disease;
Diamond-Blackfan anemia
Many antibiotics act
selectively on bacterial
ribosomes: e.g.,
tetracyclines,
aminoglycosides
(gentamicin, streptomycin)
Diseases characterized by
cytoplasmic accumulation
of misfolded proteins:
Parkinson’s
disease, Alzheimer’s
disease, Angelman
syndrome, inclusion body
myopathies
Several known glycogen-
storage diseases, including
major groups of hepatic–
hypoglycemic
and muscle-energy
pathophysiologies
Lipid storage diseases such
as Gaucher’s and
Niemann-Pick disease, liver
cirrhosis
 4. Other disorders of single enzyme deficiency

5. Disorders of lysosomal biogenesis

!
6. Disorders of the lysosomal membrane

NEC. APOP.

Actin binding proteins Functions Location Proteins

Actin- bundling proteins Cross- link actin filaments into parallel Microvillus Fascin

arrays 

Fimbrin
Provides support and imparts rigidity

Actin filament- severing Cut long actin filaments into short Gelsolin
proteins fragments - normally initiates actin
polymerization but at high Ca2
concentrations causes severing of
the actin fi laments, converting an
actin gel into a fluid state.

Actin- capping proteins Block further addition of actin Skeletal and cardiac Tropomodulin
molecules by binding to the free end of muscle cells - binds to the free end of actin
an actin filament myofilaments, regulating the length
of the filaments in a sarcomere.

Actin cross- linking Cross linking actin filaments with each Cytoskeleton of Spectrin,adductin, protein 4.1, protein 4.9
other erythrocytes

Actin motor proteins Myosin
 Muscle cells Myosin II:



 8 nm – thin filaments

Hydrolyzes ATP to provide the energy 15 nm – thick filaments
for movement along the actin filament
from the minus end to the plus end
 MICROFILAMENTS INTERMEDIATE FILAMENTS MICROTUBULES

CLINICAL CORRELATION: ABNORMALITIES IN MICROTUBULES AND FILAMENTS

1. Microtubules
a. Kartagener’s Syndrome
b. Drugs
i. Colchicine
1. Bind to tubulin molecules and prevent their polymerization
ii. Vinblastine and vincristine (oncovin)
1. Bind to microtubules and inhibit the formation of mitotic spindle
iii. Paclitaxel (Taxol)
1. Chemo for breast cancer
2. Stabilizes microtubules, preventing them from depolymerizing
2. Actin filaments
a. Cytochalasin B and D
i. Prevent actin polymerization by binding to the pkus end of the actin filament
ii. Inhibit lymphocyte migration, phagocytosis and cytokinesis
b. Phalloidin
i. Bind to actin filaments, stabilizing them and preventing them from depolymerization
ii. Prolonged exposure disruption of dynamic equilibrium cell death
Nucleostemin
- P53- binding protein in the nucleolus
- Regulates cell cycle and influences cell differentiation
- As cellular differentiation progresses, the level of this protein decreases
- Presence in malignant cells:
o Play a role in uncontrolled proliferation
Nucleolonema
- Network formed by the granular and the fibrillary materials
- Fibrillar material
o Contains ribosomal genes
o Actively undergoing transcripton
o Large amounts of rRNA
- Granular material
o Site of initial ribosomal assembly
o Contains pre-packed preribosomal particles

1. Cell Division
1.1.

Mitosis Meiosis Amitosis*

Types of cell Somatic Germ
Daughter cells 2 diploid 4 haploid
produced
Number of 46; remains the same 23; reduced by
chromosomes half
Phases PMAT 1 PMAT 1 & 2
Purpose Growth and development Passing on of
traits
Reproduction type Cellular / asexual Sexual
Pair Homologous (2 chromosomes of No homologue
each kind) pairs
*Amitosis – direct cell division by simple cleavage of nucleus, without spindle formation or appearance of chromosomes

1.1.1. Mitosis
- Requisites
o DNA replication (S Phase):
▪ Helix uncoils into 2 nucleotide chains (template) new strand binds to template strand 2 DNA molecules
are formed (1 old,1 newly assembled nucleotide strand)
o 2x normal diploid complement (92)
o Storage of energy
- Structural changes in each phase
o Interphase
▪ Nucleolus, clumps of condensed chromatin (heterochromatin) in nucleus
o Prophase
▪ Start: Appearance of chromosomes (condense, become shorter and thicker)
▪ Chromosomes: 2 parallel strands (chromatids) joined at the centromere (constricted segment)
▪ Kinetochore – trilaminar disc at centromere
▪ Centrioles replicate and migrate to opposite poles
▪ End: Breakdown of nuclear envelope
o Metaphase
▪ Start: alignment of chromosomes in middle forming equatorial plate / metaphasial plate (development of
mitotic spindle)
▪ Mitotic spindle – fusiform array of microtubules which extend from centrioles to chromosomes or pole to pole
o Anaphase
▪ Start: separation of single kinetochore of each pair of chromatid. Each now has its own.
▪ Sister chromatids (no longer bound together) move to opposite poles.
➢ Are not “pulled”, microtubules have no contractile properties
➢ MOA: microtubules shorten by depolymerization at one end or the other, at kinetochore end.
➢ Dynein motor
o Telophase
▪ Chromosomes clustered at spindle poles
▪ Segments of a nuclear envelope are formed around
▪ Chromosomes uncoil, losing their stainability
▪ End: karyokinesis is complete
! Nucleoli are recormed
! Perinuclear cisterna formed from nuclear envelope coalescence
▪ Cleavage furrow – constriction of the cytoplasm midway
! Deepens until it encounters microtubules of the spindle
▪ Daughter cells remain connected by a slender cytoplasmic bridge occupied by residual spindle microtubules
that are bound together at midpoint, forming the mid-body.
 ▪ Cytokinesis is complete: microtubules depolymerize; two halves are retracted into cytoplasm of daughter
cells
*in females, 1 x-chromosome remains condensed during interphase = sex chromatin / Barr body

- Common drugs or substances which can affect mitosis

o Interfere with assembly and disassembly of microtubules:
▪ Colchicine (anti-gout) – inhibits microtubule polymerization by binding to tubulin
− breaks down microtubules which pull apart the chromosomes; stops cell from completing mitosis;
“mitotic poison / spindle poison”
▪ Vinblastine – binds tubulin; M phase cell cycle specific
▪ Paclitaxel – arrests function of microtubules by hyperstabilizing their structure; destroys cell ability to use its
cytoskeleton; binds to the B-subunit of tubulin
▪ Griseofulvin (anti-fungal)

1.1.2. Meiosis
- 1st meiotic division – reduction division
o Prophase
▪ Leptotene – chromosomes become visible – thin, long, single strands in nucleus
▪ Zygotene – synapsis = pairing of homologous chromosomes
▪ Pachytene – chromosomes coil, become shorter and thicker; may appear as a single chromosome
▪ Diplotene – replication. Each chromosome has a pair (bivalent) with 4 chromatids
− Crossing over at chiasmata
▪ Diakinesis – shortening and thickening, chromosomes clump together at center of nucleus, nucleus
fragments and disappears
o Metaphase
▪ Nuclear membrane breaks down
▪ Spindle formation
▪ Bivalents align at equatorial plate
▪ Kinetochore does not divide
o Anaphase
▪ Whole chromosomes (not sister chromatids) separate and move to opposite poles
▪ Daughter cells = haploid
o Telophase
▪ Nuclei are briefly reconstituted
- 2nd meiotic division – genetic material is equally distributed – equational division
o Chromatids separate
o Kinetochores divide
o Sister chromatids move apart to opposite poles
- Biological significance:
a. Constancy of chromosome #
b. Genetic diversity

1.1.3. Cytogenic anomalies:

- Polyploidy – more than two sets of chromosomes (p.41)
o Klinefelder’s syndrome – 44XXY
- Aneuploidy – departure from diploid # not involving whole sets
o Turner’s Syndrome – 44XO
- Deletion – loss of a portion (p.46)
o Cri du chat – unpaired 5th chromosome
- Nondisjunction – failure to separate (meiosis)
o Down Syndrome – trisomy 21, Edwards Syndrome –18, Patau syndrome –13
- Translocation – transfer of a segment to a nonhomologous chromosme
o cancer

FACTORS THAT AFFECT RATE OF SIMPLE DIFFUSION:

1. Amount of substance available
2. Velocity of kinetic motion
3. Number of sizes or openings through which ions can move

LIMITING FACTORS OF SIMPLE DIFFUSION: (TCS)

1. Thermal agitation of the specific molecule
2. Concentration gradient across the membrane
3. Solubility of that solute (permeability coefficient)

FACTORS THAT AFFECT RATE OF FACILITATED DIFFUSION: (CACAR)

1. Concentration gradient
2. Amount of carrier available
3. Affinity of solute- carrier interaction
4. Rapidity of the conformational change for both the loaded and unloaded carrier

FACTORS THAT AFFECT NET DIFFUSION: (PETCH)

1. Permeability coefficient of the substance
2. Electric potential across the membrane
3. Temperature
4. Concentration gradient across the membrane
5. Hydrostatic pressure