mitochondria

1. MITOCHONDRIA

2. •Mitochondria are self-duplicating spherical, granular
or filamentar cell organelles.
•They are found in all eukaryotic cells, with the
exception of mature mammalian RBCs.
•They serve as the centres of aerobic respiration,
energy transduction, oxidative phosphorylation and
ATP synthesis.
•Also, they bring about the terminal oxidation of
organic fuel molecules and the transformation of their
potential chemical energy to the biologically available
potential energy of ATP molecules.

3. DISCOVERIES
• Mitochondria were first observed by Kolliker in 1880.
• Richard Altmann (1894) called them “bioplasts”, thinking that they
would be symbiotic living particles within the cell.
• In 1897, Benda used the term "mitochondria" to designate them.
• At about the same time, Michaelis suggested that mitochondria
are the centres of oxidation-reduction (redox) reactions.
• This was later on confirmed by Kingbury in 1912.
• In the late 1940s and early 1950s, Claude, Palade, Porter and
others made elaborate studies on their isolation, fixation and
sectioning.
• Studies were also in progress to determine their biochemical and
enzymatic properties, molecular architecture, biological roles and
biogenesis.

4. Albert von Kolliker

5. Location
•Usually, mitochondria are mobile organelles, uniformly
distributed within the cell.
•Still, they may often remain crowded or clustered
preferentially around certain strategic sites of maximum
energy demand.
•Thus, the distribution of mitochondria appears to be related
to their function as energy suppliers.
•In some cases, they perform active and passive movements.
•This ensures the supply of ATP wherever it is required.
•But, in some other instances, many of them are permanently
stationed in regions where more energy is needed.

6. •For example, in muscle cells, they occur in large
numbers in the l-bands; in sperm tail, they remain
wrapped around the axoneme (axial filament); in
protein synthetically active cells, they mostly remain
attached to the ER.
•The form and size of mitochondria vary with cell types,
but are characteristic for each cell type.

7. Number
• The number of mitochondria per cell varies greatly with species.
• It may range from zero to many thousand.
• In prokaryotes, mature mammalian RBCs and some colourless algae
(such as Leucothrix, Vitreoscilla, etc.), mitochondria are absent.
• Mammalian RBCs lose all their mitochondria during differentiation.
• So, they have to generate their ATP by glycolysis alone.
• However, their ATP requirement is very much reduced because of the
total absence of synthetic processes.
• There is only a single mitochondrion in some sperms, some flagellate
protozoans (e.g., Chromulina, Trypanosoma gambiense), some algae
(e.g., Micromonas), etc.
• An ordinary mammalian liver cell (hepatocyte) may contain nearly
1000-1600 mitochondria.

8. •The giant amoeba Pelomyxa has as many as 100,000
mitochondria, sea-urchin egg has up to 15,00,000, and some
oocytes may have as many as 30,00,000.
•Perhaps, the highest number of mitochondria is found in the
flight muscles of some insects (the numerous muscle
mitochondria are generally called sarcosomes).
•The cells of green plants have relatively fewer number of
mitochondria.
•In most cases, there is a direct relation between the number
of mitochondria and the metabolic state of the cell.

9. Structure
•Mitochondria are double-walled and fluid-filled bags. A
mitochondrion consists of gelatinous, enzyme-rich and
proteinaceous matrix, enveloped by two concentric
membranes.

10. (a) Mitochondrial membranes
•Mitochondrial membranes are almost fluid
films, with a compact molecular arrangement.
•They are lamellar in organization, formed of a
lipid bilayer and extrinsic and intrinsic proteins.
•In between the two membranes is the
intermembrane space.
•It is filled with a fluid, rich with enzymes and
co-enzymes.

11. •The outer membrane protects the mitochondrion
from enzymatic disintegration, and also provides
channels for the passage of solutes.
•It contains the unique intrinsic tprotein porin,
which is resistant to enzyme action.
•Porin serves as a transport protein and also forms
aqueous channels across the lipid bilayer.
•The inner membrane is the centre of oxidative
phosphorylation and ATP synthesis.

12. •The inner and outer mitochondrial membranes
differ from each other qualitatively and
quantitatively in their chemical make-up, enzymatic
composition and permeability properties.
•Usually, the lipid to protein ratio is much higher in
the outer membrane (outer membrane has 40%
lipids and 60% proteins by weight and inner
membrane has 25% lipids and 75% proteins).
•More than 60 kinds of proteins are present in the
inner membrane.

13. •Most of them are part of the molecular machinery
of electron transport chain.
•Most enzymes of the inner membrane are
respiratory.
•They include ATP synthase and those concerned
with redox reactions, oxidative phosphorylation
and ATP synthesis.
•But, the enzymes of the outer membrane are not
closely concerned with redox reactions and
oxidative phosphorylation.

15. •The outer membrane is freely permeable to
a large variety of molecules and ions, but the
inner membrane is rather impermeable to
most molecules and ions.
•The outer membrane contains the integral
transmembrane transport proteins porins.
•They form large transmembrane channels for
the passage of materials.

16. •The inner membrane contains a large number of
carrier proteins, known as translocases, and large
amounts of cardiolipin (a phospholipid).
•Translocases are involved in the transport of
metabolites, such as aspartate, glutamate,
phosphate, ATP, ADP, etc.
•Cardiolipin makes the membrane especially
permeable to ions.

17. •At certain points, the inner and outer
membranes come into close contact with
each other. Such points, are called
contact zones.
•At these points, there is high crowding of
cytoribosomes.
•So, contact zones are believed to be the
entry sites of cytoplasmic proteins to
the mitochondrial matrix.

19. •The inner membrane has several hollow infoldings into
the matrix, known as cristae or mitochondrial crests.
•They may be transverse or longitudinal, lamellar, tubular
or vesicular, and sometimes reticulate.
•Their number seems to be directly related to the
oxidative activity of the mitochondrion.
•Cristae enormously increase the surface area of the
inner membrane and provide a large number of
compartments for oxidative phosphorylation.

20. (b) ATP synthase (ATP synthetase or ATPase)
•Attached to the cristae and inner membrane are numerous
regularly spaced and stalked lollipop-like particles, formerly
called elementary particles, F₁ - F0 particles, oxysomes, or
Fernandez-Moran sub-units.
•Now, they are more appropriately called ATP synthases, or
mitochondrial ATPases.
•They are the enzymes, involved in the coupling of redox
reactions with phosphorylation reactions, and the synthesis
of ATP.
•For elucidating the structure and function of ATP synthases,
Paul Boyer and John Walker were awarded the Nobel Prize in
Chemistry in 1997

21. •ATP synthase is a complex, multiunit,
transmembrane protein cluster that spans the inner
mitochondrial membrane.
•It has three parts, namely base piece, stalk and
head piece.
•Base piece, or F0 particle or F0 unit, is a hydrophobic
component and it remains embedded in the inner
mitochondrial membrane.
•It is formed of 10 to 20 sub-units of polypeptides
and proteolipids.
•It forms a proton channel for proton translocation.

22. •Stalk (F5-F6 particle) is formed of three polypeptide
sub-units, namely one gamma chain, one delta
chain and one epsilon chain.
•Also, it contains olygomycin-sensitivity conferring
proteins (OSCP), which are essential for the binding
of the F, particle with the mitochondrial membrane.
•Head piece (F, particle) is hydrophilic and capped by
an ATPase inhibitor protein.
•It is formed of six sub-units or polypeptides, namely
3 alpha chains and 3 beta chains.

24. •The inner membrane and the cristae contain all components
oxidative phosphorylation (ATP synthesising) system.
•The appear to exist in five complexes (Green - 1964).
•Complex I & II lie in the base piece of ATP synthase, complex
III in the stalk and complexes IV & V in the head piece.
•Complexes I to IV are the constituents of the respiratory
chain.
•But, the fifth one is concerned with the transfer and
conservation of energy and the synthesis of ATP.
•The electron carriers co-enzyme Q (CoQ) or ubiquinone (UQ)
and cytochrome-C serve as mobile molecules - CoQ between
complexes I and III, and II and III, and cytochrome-C between
complexes III and IV.

26. (c) Matrix
•Mitochondrial matrix is a dense, gel-like and protein-
rich substance.
•It contains high concentrations of enzymes, multiple
copies (usually 2-6 copies) of circular mitochondrial DNA
(mtDNA), mRNA and tRNA, numerous ribosomes
(mitoribosomes) and a variety of crystals, granules, fibrils
and tubules.
•The major enzymes of the mitochondrial matrix include
the enzymes involved in the synthesis of nucleic acids
and proteins, the enzymes of fatty acid oxidation, and
the enzymes of the TCA cycle.

27. •Most of the matrix enzymes are oxidative or
respiratory, some are synthetic, and no one is
digestive.
•With the exception of succinic acid dehydrogenase
(the enzyme which converts succinic acid to
fumaric acid), all enzymes of the TCA cycle are
freely distributed in the mitochondrial matrix;
succinic acid dehydrogenase is located in the inner
membrane.
•The synthetic enzymes are involved in the
mitochondrial synthesis of DNA, RNAs and proteins.

28. •Mitochondrial DNA is self-duplicating and it stores
the information required for the growth and
duplication of mitochondria.
•Mitochondrial granules contain phospholipids, yolk
bodies, glycogen deposits, insoluble inorganic salts,
etc.
•They are believed to be involved in the uptake and
storage of Ca+, Mg and other divalent ions.

29. Chemical composition
•Mitochondria are formed mainly of water, proteins, lipids,
DNA, RNAs, oxidative and synthetic enzymes and metallic
ions.
•Quantitatively, water is the most predominant constituent.
•It plays an important role in enzymatic actions, and also
serves as the physical medium for the diffusion of
metabolites among the enzyme systems.
•Proteins are the major organic constituents.
•In most cases, nearly 4% of them are found in the outer
membrane, 21% in the inner membrane, 67% in the matrix,
and the rest in the intermembrane space.
•But, in some cases nearly 60% of the proteins may be found
in the inner membrane.

30. •Mitochondrial proteins are of two groups, soluble and
insoluble.
•Soluble proteins mainly include the enzymes of the matrix
and some extrinsic membrane proteins.
•Insoluble proteins include the intrinsic membrane proteins.
•Some of them are functional, and the others structural.
•The lipid constituents of mitochondria include phospholipids,
cholesterol and free fatty acids.
•Phospholipids amount to nearly 75% of the lipid content.
•Phospholipids, such as phosphatidyl choline, phosphatidyl
ethanolamine and cardiolipin, are found in significantly high
levels.

31. •Usually, cholesterol occurs in small amounts.
•The abundance of cardiolipin and the dearth
of cholesterol make the mitochondrial
membrane distinct from other
biomembranes.
•The high phospholipid content in the
mitochondrial membrane promotes the
functioning of the respiratory chain and other
redox molecules.

32. •In general, the amount of phospholipids is three times
greater, and that of cholestrol six times greater in the outer
membrane than in the inner membrane.
•But, the amount of cardiolipin is much higher in the inner
membrane.
•The structural and functional significance of this differential
distribution of lipids in the two membranes is not clearly
understood.
•In addition to proteins and lipids, some other organic
molecules are also found in the mitochondria.
•Most of them are redox molecules, involved in electron
transport and oxidation-reduction reactions. They include
ubiquinones, flavins (FMN, FAD) and pyridine nucleotides
(NAD).
•These are seen mostly associated with the inner membrane.

33. Mitochondrial DNA (mtDNA)
•mtDNA is double-stranded and circular.
•It is a covalently closed circle, occurring in multiple copies.
•Most usually, it remains attached to the inner mitochondrial
membrane within the mitochondrial matrix.
•The function of mtDNA is similar to that of the
chromosomal DNA of eukaryotes.
•It stores the biological information, required for the growth
and multiplication of mitochondria.
•It can undergo self-duplication or replication to produce its
own copies.
•It can also undergo transcription and translation to produce
rRNA, tRNA, mRNA and proteins.

34. •However, it is not absolutely autonomous or
independent in carrying out these functions.
•It depends upon the nuclear DNA for the
necessary enzymes and protein factors that
are essential for its duplication, transcription
and translation.
•These enzymes and proteins factors are
coded by the chromosomal DNA and are
synthesised in cytoplasmic ribosomes.
•They are finally transported to the
mitochondrial matrix.