Mitochondria

Mitochondria is a double membraned cell organelle found in cytoplasm of eukaryotes. This energy
producing organelle is called the “Power house of the cell”. The name “mitochondria” is from Latin
where “mito” means thread and “chondria” means granular body. They are the main site of cellular
respiration in aerobic organisms. They are an example for semi-autonomous organelle along with
chloroplast due to the presence of its own DNA.
The organelle was first observed by Richard Altman in 1894. The term “Mitochondria” was coined by
Carl Benda in 1898.This organelle also produces enzymes for conversion of food to energy.

Endosymbiotic theory
It is believed that the mitochondria and chloroplast evolved from bacteria like prokaryotes, which were
engulfed by the eukaryotic cell billions of years ago, then they developed a symbiotic relationship with
the eukaryotic cell. This explains why mitochondria and chloroplast contain their own DNA which
codes for some protein. After this method of taken up by a host cell, the organelles have lost most of
their own DNA and have become dependent on the proteins which are encoded by the nuclear genome.
Conversely, the host cell has become dependent on these organisms for their ATP requirements.
According to this hypothesis the energy producing organelles might have been prokaryotes engulfed by
eukaryotes and subsequent establishment with the host cells is called endosymbiotic theory.

Structure and distribution

Mitochondria is a semi-autonomous cell organelle seen in eukaryotic cells. They constantly change
their shape. They move about the cell with the help of microtubules. The form, size and number of
mitochondria depend on the type of cell. They are abundant in heart cells and few in liver cells.The size
of the mitochondria ranges from 0.5-1 micro meter in diameter and is sausage shaped. In fibroblasts, the
shape of the mitochondria is elongated and thread-like. The number of mitochondria in a liver cell is
about 1500.

Mitochondria can be seen as granules or rods or filaments under the light microscope. But under the
electron microscope, it appears as a complex double membraned organelle, the outer and inner
membrane, intermembrane space and internal matrix. The two membranes are highly specified for the
organelle’s complex function- oxidative phosphorylation leading to ATP synthesis.

The double membrane can be described as a larger wrinkled bag inside a smaller unwrinkled bag. The
two membranes create 3 compartments which differ in structure and function. The outer membrane
consists of numerous integral protein- porin, which are large transport protein which form large
aqueous channels through lipid bilayer. The inner membrane is a much more specialized membrane
which makes the membrane permeable to ions. It carries transport protein that makes it selectively
permeable to small molecules. The membrane is folded to form cristae, which increases inside the cell.
The cristae increase in high energy requirement cells like heart cells and decreases in low energy
requirement cells like liver cells. The inner membrane contains vital protein complexes like enzyme
complexes in ETC which are essential for oxidative phosphorylation and ATP synthesis.

The mitochondrial matrix consists of several enzymes. It also contains mitochondrial DNA,70s
mitochondrial ribosomes and tRNA, etc. The enzymes in the matrix include those that are involved in
TCA cycle. The main end products of this cycle are CO2, NADH and FADH2. NADH and FADH2 are
the main source of energy in ETC.

Functions of mitochondria
Mitochondria is called the power house of the cell as it converts nutrients into energy- yielding
molecule ATP to fuel the cell activities. This function is known as aerobic respiration. It involves
glycolysis, Krebs cycle and ETC. the events that occur in mitochondria are
1. Mitochondrial oxidation(matrix)
2. ETC (mitochondrial membrane)

Mitochondrial oxidation
It occurs in the matrix, except for the conversion of succinate to fumarate, which occurs in
mitochondrial membrane. It begins with the transport of pyruvate and fatty acids selectively transported
from cytosol to mitochondrial matrix to form acetyl co-A, a two Carbon compound. This compound
enters the TCA cycle, as a result of which 2 molecules of CO2, 3NADH,1GTP, 1FADH2, and 3H+ are
generated.
Acy Co-A +2 H20 +3 NAD +FAD = 2 CO2 +3 NADH + FADH+
3H+

The significance of TCA is the release of high energy electrons of acetyl co-A. These electrons are held
by NADH and FADH2 from where they are passed to respiratory chain in inner mitochondrial
membrane resulting in ATP synthesis.

Electron Transport Chain (ETC)

It consists of a series of electron carriers located in the inner mitochondrial membrane. These electron
carriers are complex proteinswhich are arranged in the order of their reducing redox potential. The
electrons are passed from NADH or FADH2 into the ETC. the various electron carriers are arranged
into 4 complexes, I, II, III, IV. Two other carriers, Ubiquinone and cytochrome C are independently
situated within or on the

membrane between the large immobile comple

When NADH is the electron donor, electron enters the respiratory chain complex 1, transfer the electron
to UBQ. When FADH2 is the donor the e- is transferred directly from complex 2 to UBQ.The free
energy released by the downhill transport of the e- is used for the translocation of the H+ from matrix to
intermembrane space. The translocation of protons due to these electron transporting complexes
establishes a proton gradient that establishes phosphorylation of ADP into ATP. The e- transport
complex transports the e- through the chain, converting the final acceptor O2 into H2O, attaching with
hydrogen, generating energy producing molecules ATP, by oxidizing NADH and FADH2 to NAD+
and FAD+.

Complex 1- NADH dehydrogenase :- It is a huge protein complex combining of 40 protein subunits

FMN nucleotide and numerous Fe-S centers. It translocates 4H+ into the intermembrane space per
NADH. It transports e- from NADH to UBQ.
Complex 3 – cytochrome (oxido-reductase) :- It transfers e- from reduced UBQ. It consists of 3
cytochrome centers- cyt B and Cyt C1 and one Fe-S center. It transports 4H+ and 2e-. it transfers the e-
to cyt C, which carries only one e- at a time.
Complex 4 – cytochrome oxidase :- it receives e- from reduced cyt c and reduces O2 into H2O. it
contains 13 protein subunits, 2 cytochromes ( a and a3), and one copper site. It translocates 2H+,
transfers 2e- and also consumes 2e- from matrix in generating one molecule of H2O from ½ molecule
of O2.
Complex 2- succinate dehydrogenase :- it is a protein complex of 4 protein subunits. It catalyzes the key
reaction of TCA. It transfers e- to UBQ. Unlike complex 1, complex 2 does not transport H+ into
intermediate space. Therefore complex 2 contributes less energy to ETC.
The e- transfer is completed with H+ pump which pumps out H+ from matrix to intermembrane space
by which an electro-chemical proton gradient is created accross the membrane. ATP synthase(complex
5) of ETC translocates H+ from intermembrane space to matrix producing ATP.

Oxidative phosphorylation
The chemiosmotic hypothesis was proposed by Peter Michel in 1961 to explain the generation of ATP
by oxidative phosphorylation. According to this hypothesis, the high energy chemical molecules are
formed as a result of a link between chemical transport process (chemi- chemical, osmos- push)

The mitochondrial respiratory chain in the inner membrane is proton translocating. It pumps out H+
from the matrix at 3 sites if the donor is NADH and 2 sites if the donor is a FADH 2 . In NADH, the 3
sides of H+ pump are complex one, complex 3 and complex 4 With 4 H+ at complex 1 and 3 and 2H+
at complex 4. This is brought about by the energy released by the high energy electron, as they are
transported from one carrier molecule to the other in the respiratory chain. As a result, an
electrochemical proton gradient is created across the membrane. The membrane bound enzyme; ATP
synthase can translocate H+ across the membrane from intermembrane space to matrix. The back flow
of H+ down this gradient is inturn used to drive the ATP synthase to catalyse the conversion of ADP
+iPto ATP

ATP synthase is seen as particles projecting into the matrix from the inner membrane which were
formerly known as oxysomes. It has transmembrane portion, basal plate which serves as a electron
carrier, a stalk and F1 ATPase portion it can also work in opposite direction and hydrolyses ATP to
ADP+iP.

Biosynthesis of mitochondria
Mitochondria and chloroplast serve as semiautonomous organelles which possess DNA, ribosomes
(70s) and complete set of protein synthesising machinery. But the Biogenesis of these organelles is
highly dependent on the nuclear genome. Though, they are self-replicating, Biogenesis occurs by
integrated activity of both nuclear genome and the genome of these organelles.
They grow by importing most of their proteins from cytoplasm and by internal synthesis of some
proteins and replication of the genome. Similar to cells, mitochondria divide and fuses with other
mitochondria, maintaining their number of cells.
These organelles arise by the growth and division of existing mitochondria or chloroplast. The division
begins by furrowing of the inner membrane followed by the outer membrane. The replication of
mitochondrial DNA occurs preparatory to the division of the organelle. Mitochondrial DNA replication
and division occurs out of phase with the cell cycle. Organelle DNA replication occurs at random
according to the need of the cells.
Example - a large increase is seen if skeletal muscle is stimulated to contract for prolonged period.