Mitochondrion
In
cell biology, a
mitochondrion (plural
mitochondria) (from
Greek μιτος or
mitos, thread +
κουδριον or
khondrion, granule) is an
organelle, variants of which are found in most
eukaryotic cells.
Mitochondria are sometimes described as "cellular
power plants," because they convert organic materials into energy in the form of
ATP via the process of
oxidative phosphorylation. Usually a cell has hundreds or thousands of mitochondria, which can occupy up to 25% of the cell's
cytoplasm. Mitochondria have
their own DNA and may, according to the
endosymbiotic theory, be descended from free-living
prokaryotes that were closely related to
rickettsia bacteria.
|
Simplified structure of a typical mitochondrion |
A mitochondrion contains outer and inner membranes composed of
phospholipid bilayers and
proteins. The two membranes, however, have different properties. Because of this double-membraned organization, there are 5 distinct compartments within mitochondria. There is the outer membrane, the intermembrane space (the space between the outer and inner membranes), the inner membrane, the cristae space (formed by infoldings of the inner membrane), and the matrix (space within the inner membrane).
Outer membrane
The outer mitochondrial membrane, which encloses the entire organelle, has a protein-to-phospholipid ratio similar to the eukaryotic plasma membrane (about 1:1 by weight). It contains numerous
integral proteins called
porins, which contain a relatively large internal channel (about 2-3
nm) that is permeable to all molecules of 5000
daltons or less.
Larger molecules can only traverse the outer membrane by
active transport. It also contains
enzymes involved in such diverse activities as the elongation of
fatty acids,
oxidation of
epinephrine (adrenaline), and the
degradation of
tryptophan.
Inner membrane
The inner mitochondrial membrane contains proteins with four types of functions:
# Those that carry out the oxidation reactions of the respiratory chain.#
ATP synthase, which makes
ATP in the matrix.# Specific transport proteins that regulate the passage of
metabolites into and out of the matrix.# Protein import machinery.It contains more than 100 different
polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). Additionally, the inner membrane is rich in an unusual phospholipid,
cardiolipin, which is usually characteristic of bacterial plasma membranes. Unlike the outer membrane, the inner membrane does not contain porins, and is highly impermeable; almost all ions and molecules require special membrane transporters to enter or exit the matrix. In addition, there is a membrane potential across the inner membrane.
The inner mitochondrial membrane is compartmentalized into numerous
cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to generate ATP. In typical
liver mitochondria, for example, the surface area, including cristae, is about five times that of the outer membrane. Mitochondria of cells which have greater demand for ATP, such as muscle cells, contain more cristae than typical liver mitochondria.
Mitochondrial matrix
|
Image of cristae in rat liver mitochondrion |
The matrix is the space enclosed by the inner membrane. The matrix contains a highly concentrated mixture of hundreds of enzymes, in addition to the 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 possess their own genetic material, and the machinery to manufacture their own
RNAs and
proteins. (
See: protein synthesis). This nonchromosomal DNA encodes a small number of mitochondrial
peptides (13 in humans) that are integrated into the inner mitochondrial membrane, along with
polypeptides encoded by
genes that reside in the host cell's
nucleus.
Although it is well known that the mitochondria convert organic materials into cellular energy in the form of
ATP, mitochondria play an important role in many
metabolic tasks, such as:
*
Apoptosis-programmed cell death
*
Glutamate-mediated excitotoxic
neuronal injury
* Cellular proliferation
* Regulation of the cellular
redox state
*
Heme synthesis
*
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.
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 oxidising the major products of
glycolysis:
pyruvate and
NADH that are produced in the cytosol. This process of
cellular respiration, also known as
aerobic respiration, is dependant on the presence of
oxygen. When oxygen is limiting the glycolytic products will be metabolised by
anaerobic respiration a process that is independent of the mitochondria. The production of ATP from glucose has an approximately 15 fold higher yield during aerobic respiration compared to anaerobic respiration.
Pyruvate: 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 oxidised and combined with
coenzyme A to form CO
2,
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. The citric acid cycle oxidises 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 FADH
2 is transferred to oxygen (O
2) in several steps via the electron transport chain.
Protein complexes in the inner membrane (
NADH dehydrogenase,
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 leak prematurely to oxygen, forming the toxic free radical superoxide. This can cause oxidative damage 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 built 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 (P
i). 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 mitochondial 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, mediated by a proton channel called
thermogenin. This results in the unharnessed potential energy of the proton electrochemical gradient being released as heat. Thermogenin is found in
brown adipose tissue (brown in colour due to high levels of mitochondria) where it is used to generate heat by non-shivering thermogenesis. Non-shivering thermogenesis is the primary means of heat generation in newborn or
hibernating mammals.
As mitochondria contain ribosomes and DNA, and are only formed by the division of other mitochondria, it is generally accepted that they were originally derived from
endosymbiotic prokaryotes. Studies of
mitochondrial DNA, which is often circular and employs a variant
genetic code, show their ancestor, the so-called
proto-mitochondrion, was a member of the
Proteobacteria.
In particular, the pre-mitochondrion was probably related to the
rickettsias, although the exact position of the ancestor of mitochondria among the alpha-proteobacteria remains controversial. The endosymbiotic hypothesis suggests that mitochondria descended from specialized bacteria (probably purple nonsulfur bacteria) that somehow survived
endocytosis by another species of prokaryote or some other cell type, and became incorporated into the
cytoplasm. The ability of symbiont bacteria to conduct cellular respiration in host cells that had relied on
glycolysis and fermentation would have provided a considerable evolutionary advantage. Similarly, host cells with symbiotic bacteria capable of
photosynthesis would also have an advantage. In both cases, the number of environments in which the cells could survive would have been greatly expanded.
This relationship developed at least 2 billion years ago and mitochondria still show some signs of their ancient origin. Mitochondrial
ribosomes are the 70S (bacterial) type, in contrast to the 80S ribosomes found elsewhere in the cell. 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 mature mRNAs. Unlike their nuclear cousins, mitochondrial genes are small, generally lacking
introns, and many chromosomes are circular, conforming to the bacterial pattern.
A few groups of unicellular eukaryotes lack mitochondria: the
microsporidians,
metamonads, and
archamoebae. On
rRNA trees these groups appeared as the most primitive eukaryotes, suggesting they appeared before the origin of mitochondria, but this is now known to be an artifact of
long branch attraction " they are apparently derived groups and retain genes or organelles derived from mitochondria (e.g.
mitosomes and
hydrogenosomes).
There are no primitively amitochondriate eukaryotes, and so the origin of mitochondria may have played a critical part in the development of eukaryotic cells.
Mitochondria replicate their DNA and divide mainly in response to the energy needs of the cell; in other words their growth and division is not linked to 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. At cell division, mitochondria are distributed to the daughter cells more or less randomly during the division of the
cytoplasm. Mitochondria divide by binary fission similar to bacterial cell division. Unlike bacteria, however, mitochondria can also fuse with other mitochondria. Sometimes new mitochondria are synthesized in centers that are rich in the
proteins and
polysomes needed for their synthesis.
Mitochondrial genes are not inherited by the same mechanism as nuclear genes. At fertilization of an egg 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 comes from the egg only. Sperm cells contain a single spiral mitochondrion that is used to provide the energy needed for its swimming behavior. The sperm's mitochondria enters the egg, but are almost always destroyed and do not contribute their genes to the embryo.
[Kimball, J.W. (2006) "Sexual Reproduction in Humans: Copulation and Fertilization," Kimball's Biology Pages (based on Biology, 6th ed., 1996)]] Paternal sperm mitochondria are marked with
ubiquitin to select them for later destruction inside the
embryo.
[}} Discussed in Science News.] The egg contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. Mitochondria are, in most cases, inherited down the female line.
This
maternal inheritance of mitochondrial DNA is seen in most organisms, including all animals. However, mitochondria in some species can sometimes be inherited through the father. This is the norm amongst certain
coniferous plants (although not in pines and yew trees).
It has been suggested to occur at a very low level in humans.
Uniparental inheritance means that there is little opportunity for
genetic recombination between different lineages of mitochondria. For this reason, mitochondrial DNA is usually thought of as reproducing by
binary fission. However, there are several claims of recombination in mitochondrial DNA, most controversially in humans. 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.
Mitochondrial genomes have many fewer genes than do the related eubacteria from which they are thought to be descended. Although some have been lost altogether, many seem to have been transferred to the nucleus. This is thought to be relatively common over evolutionary time. A few organisms, such as
Cryptosporidium, actually have mitochondria which lack any DNA, presumably because all their genes have either been lost or transferred.
The uniparental inheritance of mitochondria is thought to result in
intragenomic conflict, such as seen in the petite mutant mitochondria of some yeast species. It is possible that the evolution of separate male and female sexes is a mechanism to resolve this
organelle conflict.
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 only reflects the history of females in a population, and so may not give a representative picture of the history of the population as a whole. For example, if dispersal is primarily undertaken by males, this will not be picked up by mitochondrial studies. This can be partially overcome by the use of patrilineal genetic sequences, if they are available (in mammals the non-recombining region of the
Y-chromosome provides such a source). More broadly, only studies that also include
nuclear DNA can provide a comprehensive evolutionary history of a population; unfortunately, genetic recombination means that these studies can be difficult to analyse.
* The
midi-clorians of the
Star Wars universe are fictional life-forms inside cells that provide
the Force. George Lucas took inspiration from the
endosymbiotic theory.
* Madeleine L'Engle's novel
A Wind in the Door posits fictional "farandolae" which are to mitochondria what mitochondria are to cells.
* In
Hideaki Sena's novel
Parasite Eve (and the video game based on it), mitochondria are independent organisms, using animals and plants as a form of "transportation," causing a major biological disaster when they decide to set themselves free.
*
*
*
Arthropod mitochondira*
Mitochondra Atlas*
Mitochondria: Architecture dictates function*
Mitochondira links*
Mitochondrion Reconstructed by Electron Tomography*
Mitochondrion with Cell Biology*
Review of evidence addressing whether mitochondria form cellular networks or exist as discrete organelles*
Video Clip of Rat-liver Mitochondrion from Cryo-electron Tomography*
Anti-mitochondrial antibodies*
Chemiosmotic hypothesis*
Chloroplast*
Electrochemical potential*
Endosymbiotic theory*
Glycolysis*
Mitochondrial disease*
Mitochondrial DNA*
Mitochondrial genetics*
Mitochondrial permeability transition pore*
Submitochondrial particle
