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Mitochondrion

2007 Schools Wikipedia Selection. Related subjects: General Biology

   Electron micrograph of a mitochondrion showing its mitochondrial matrix
   and membranes
   Electron micrograph of a mitochondrion showing its mitochondrial matrix
   and membranes

   In cell biology, a mitochondrion (plural mitochondria) (from Greek
   μιτος or mitos, thread + κουδριον or khondrion, granule) is a
   membrane-enclosed organelle, found in most eukaryotic cells.
   Mitochondria are sometimes described as "cellular power plants,"
   because they convert food molecules into energy in the form of ATP via
   the process of oxidative phosphorylation. A typical eukaryotic cell
   contains about 2,000 mitochondria, which occupy roughly one fifth of
   its total volume. Mitochondria contain DNA that is independent of the
   DNA located in the cell nucleus. According to the endosymbiotic theory,
   mitochondria are descended from free-living prokaryotes.

Mitochondrion structure

   Simplified structure of a typical mitochondrion
   Enlarge
   Simplified structure of a typical mitochondrion

   A mitochondrion contains inner and outer 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). Mitochondria range from 1 to 10 micrometers (μm) in
   size.

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:
    1. Those that carry out the oxidation reactions of the respiratory
       chain.
    2. ATP synthase, which makes ATP in the matrix.
    3. Specific transport proteins that regulate the passage of
       metabolites into and out of the matrix.
    4. 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
   Enlarge
   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 proteins encoded by genes that reside in the host cell's
   nucleus.

Mitochondrial functions

   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 dependent
   on the presence of oxygen. When oxygen is limited 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 oxidized 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 FADH[2]), 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 FADH[2]: 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. 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. 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 prematurely reduce
   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 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 (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 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, 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.

Storage for 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 store free calcium, a process that is one important event
   for the homestasis of calcium in the cell. Release of this calcium back
   into the cells interior can initiate calcium spikes or waves. These
   events coordinate processes such as neurotransmitter release in nerve
   cells and release of hormones in endocrine cells.

Origin

   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 non-sulfur 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.

Replication and gene inheritance

   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. The sperm's mitochondria enters
   the egg, but are almost always destroyed and do not contribute their
   genes to the embryo. Paternal sperm mitochondria are marked with
   ubiquitin to select them for later destruction inside the embryo. 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, therefore, 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.

Use in 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 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.

Fiction

     * 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.

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