Difference between revisions of "Mitochondrion" - New World Encyclopedia

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A '''mitochondrion''' (plural '''mitochondria''') is an [[organelle]] found in most [[eukaryote|eukaryotic]] [[cell (biology)|cells]]. Mitochondria are sometimes described as "[[cell (biology)|cellular]] power plants," because their primary function is to convert organic materials into [[energy]] in the form of [[adenosine triphosphate|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]]. The name comes from the [Greek language|Greek]]* ''mitos'', meaning "thread" and ''khondrion'', meaning "granule."
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A '''mitochondrion''' (plural '''mitochondria''') is an organelle found in most [[eukaryote|eukaryotic]] [[cell (biology)|cells]]. Mitochondria are sometimes described as "cellular power plants," because their primary function is to convert organic materials into [[energy]] in the form of [[adenosine triphosphate|ATP]] via the process of [[oxidative phosphorylation]]. Usually a cell has hundreds or thousands of mitochondria, which can occupy up to 25 percent of the cell's [[cytoplasm]]. The name comes from the [[Greek language|Greek]] ''mitos'', meaning "thread" and ''khondrion'', meaning "granule."
 
 
Mitochondria have their own [[DNA]], and, according to the generally accepted endosymbiotic theory, they were originally derived from external organisms. This shows a unique aspect of creation — the unity, etc.
 
  
 +
Mitochondria have their own [[DNA]], and, according to the generally accepted [[Mitochondrion#Origin|endosymbiotic theory]], they were originally derived from external organisms. This theory, which was popularized by Lynn Margulis, fits her view that "Life did not take over the globe by combat, but by networking" (Margulis and Sagan 1986)—in other words, by cooperation rather than Darwinian competition.
  
 
==Mitochondrion structure==
 
==Mitochondrion structure==
A mitochondrion contains outer and inner membranes composed of phospholipid bilayers studded with [[protein]]s, much like a typical [[cell membrane]]. The two membranes, however, have very different properties.  
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A mitochondrion comprises outer and inner membranes composed of phospholipid bilayers studded with [[protein]]s, much like a typical [[cell membrane]]. The two membranes, however, have very different properties.  
  
The outer mitochondrial membrane, which encloses the entire organelle, contains numerous integral proteins called ''porins'', which contain a relatively large internal channel (about 2-3 nanometers) that is permeable to all molecules of 5000 daltons (a unit of atomic mass) or less (Alberts 1994). Larger molecules can only tranverse the outer membrane by active transport (transported aided by a protein and requiring the input of chemical energy). The outer mitochondrial membrane is composed of about 50% [[phospholipid]]s by weight and contains a variety of [[enzyme]]s involved in such diverse activities as the the elongation of [[fatty acid]]s, [[oxidation]] of [[epinephrine]] (adrenaline), and the [[degradation]] of [[tryptophan]] (an essential amino acid).
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The outer mitochondrial membrane, which encloses the entire organelle, comprises by weight about 50 percent [[phospholipid]]s forming the membranous structure within which float a variety of [[enzyme]]s involved in such diverse activities as the elongation of [[fatty acid]]s, [[oxidation]] of epinephrine (adrenaline), and the degradation of tryptophan (an essential amino acid). Also floating in the membrane are numerous integral proteins called ''porins'' whose relatively large internal channel (about 2-3 nanometers) is permeable to all molecules of 5,000 [[dalton]]s (a unit of atomic mass) or less (Alberts 1994). Larger molecules can only transverse the outer membrane by active transport (transport aided by a protein and requiring the input of chemical energy).  
  
The inner membrane contains proteins with three types of functions (Alberts 1994):  
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Unlike the relatively smoothly curved outer membrane, the inner membrane is recursively invaginated, compacting a large membrane surface area into a small volume. In addition to the essential phospholipid foundation needed for forming a biological membrane, the inner membrane also comprises proteins with three types of functions (Alberts 1994):  
# those that carry out the oxidation reactions of the respiratory chain;
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# Carrying out the oxidation reactions of the respiratory chain.
# ATP synthase, which makes [[Adenosine triphosphate|ATP]] in the matrix;
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# Making [[Adenosine triphosphate|ATP]] in the [[Mitochondrion#The mitochondrial matrix|matrix]].
# specific transport proteins that regulate the passage of metabolites (intermediates and products of metabolism) into and out of the matrix.
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# Transporting proteins that regulate the passage of metabolites (intermediates and products of metabolism) into and out of the matrix.
  
It contains more than 100 different [[polypeptide]]s, 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 [[bacteria]]l 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.
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The inner membrane comprises more than one hundred different [[polypeptide]]s and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about one protein per 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.
  
 
[[image:Mitochondrie.svg|thumb|300px|
 
[[image:Mitochondrie.svg|thumb|300px|
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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]], transfer RNA (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]] (Alberts 1994).
 
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]], transfer RNA (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]] (Alberts 1994).
  
Thus, mitochondria possess their own genetic material, and the machinery to manufacture their own [[RNA]]s and [[protein]]s. This nonchromosomal DNA encodes a small number of mitochondrial [[peptides]] (13 in humans) that are integrated into the inner mitochondrial membrane, along with [[polypeptide]]*s encoded by [[gene]]s that reside in the host cell's nucleus.
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Thus, mitochondria possess their own genetic material, and the machinery to manufacture their own [[RNA]]s and [[protein]]s. This nonchromosomal DNA encodes a small number of mitochondrial [[peptides]] (13 in humans) that are integrated into the inner mitochondrial membrane, along with [[polypeptide]]s encoded by [[gene]]s that reside in the host cell's nucleus.
  
 
==Mitochondrial functions==
 
==Mitochondrial functions==
The primary function of mitochondria is to convert organic materials into cellular energy in the form of [[adenosine triphosphate|ATP]]. Notably, the inner mitochondrial membrane is folded into numerous cristae (see diagram above), 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 even more cristae than typical liver mitochondria.
+
The primary function of mitochondria is to convert organic materials into cellular energy in the form of [[adenosine triphosphate|ATP]]. Notably, the inner mitochondrial membrane is folded into numerous cristae (see diagram above), 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 that have greater demand for ATP, such as [[muscle]] cells, contain even more cristae than typical liver mitochondria.
  
 
Mitochondria play an important role in other [[metabolism|metabolic]] tasks:  
 
Mitochondria play an important role in other [[metabolism|metabolic]] tasks:  
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* [[Glutamate]]-mediated excitotoxic [[neuron|neuronal]] injury
 
* [[Glutamate]]-mediated excitotoxic [[neuron|neuronal]] injury
 
* Cellular proliferation
 
* Cellular proliferation
* Regulation of the cellular redox state (chemical process in which oxidation number of atoms is changed)
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* Regulation of the cellular redox state (chemical process in which the oxidation number of atoms is changed)
 
* [[Heme]] synthesis
 
* [[Heme]] synthesis
 
* [[Steroid]] synthesis
 
* [[Steroid]] synthesis
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===Energy conversion===
 
===Energy conversion===
As stated above, the primary function of the mitochondria is the production of [[Adenosine triphosphate|ATP]]. Outside the mitochondrion, cells can generate ATP in the absence of oxygen; this process is called [[glycolysis]]. Through glycolysis, one molecule of glucose is converted to pyruvate, producing four ATP. Inside the mitochondrion, however, much more energy is extracted. This is done by metabolizing the major products of glycolysis: [[pyruvate]] and NADH (an important coenzyme, the reduced form of nicotinamide adenine dinucleotide). This metabolism can be performed in two very different ways, depending on the type of cell and the presence or absence of [[oxygen]].  
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{{main|Citric acid cycle}}
 +
 
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As stated above, the primary function of the mitochondria is the production of [[Adenosine triphosphate|ATP]]. Outside the mitochondria, cells can generate ATP in the absence of oxygen; this process is called [[glycolysis]]. Through glycolysis, one molecule of [[glucose]] is converted to pyruvate, producing four ATP. Inside the mitochondria, however, much more energy is extracted. This is done by metabolizing the major products of glycolysis: [[pyruvate]] and [[NADH]] (an important coenzyme, the reduced form of nicotinamide adenine dinucleotide). This metabolism can be performed in two very different ways, depending on the type of cell and the presence or absence of [[oxygen]].
 +
 
 +
Inside the matrix, the citric acid cycle takes place. The citric acid cycle does not use oxygen. Each pyruvate molecule produced by glycolysis is actively transported across the inner mitochondrial membrane, and into the matrix where it is combined with coenzyme A to form acetyl CoA. Once formed, acetyl CoA is fed into the ''[[citric acid cycle]]'' , also known as the ''tricarboxylic acid (TCA) cycle'' or ''Krebs cycle''. This process creates 3 molecules of NADH and 1 molecule of [[FADH]]<sub>2</sub>, which go on to participate in the next stage, [[oxidative phosphorylation]], which involves oxygen.  
  
====Pyruvate: the citric acid cycle====
+
The energy from NADH and FADH<sub>2</sub> is transferred to oxygen (O<sub><small>2</small></sub>) in several steps via the electron transfer chain. The protein complexes in the inner membrane (NADH dehydrogenase, cytochrome c reductase, cytochrome c oxidase) that perform the transfer use the released energy to pump [[proton]]s (H<sup>+</sup>) against a gradient (the concentration of protons in the intermembrane space is higher than that in the matrix).
{{main|citric acid cycle}}
 
  
Inside the matrix the citric acid cycle takes place. The pyruvate is modified in a stepwise fashion, during which hydrogen ions are released. The hydrogen ions are picked up by carrier molecules nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD+).  These carrier molecules ferry the hydrogen ions to the inner membrane, where the enzyme ATP synthase uses the energy in the hydrogen ions to convert ADP plus a phosphate to ATP. The hydrogen ions are pumped across the membrane to combine with oxygen to produce water. This process depends on a gradient of hydrogen ions between one side of the membrane and the other. If oxygen is depleted, the hydrogen ions build up on the other side of the membrane, and the process shuts down. This process is called [[chemiosmosis]] and is an example of [[facilitated diffusion]]. [[Peter D. Mitchell|Peter Mitchell]] was awarded the 1978 [[Nobel Prize]] in Chemistry for his work on chemiosmosis. 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.
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As the proton concentration increases in the intermembrane space, a strong ''concentration gradient'' is built up. The main exit for these protons is through the ''ATP synthase'' complex. By transporting protons from the intermembrane space back into the matrix, the ATP synthase complex can make [[Adenosine triphosphate|ATP]] from ADP and inorganic phosphate (P<sub>i</sub>). This process is called [[chemiosmosis]] and is an example of facilitated diffusion. Peter Mitchell was awarded the 1978 [[Nobel Prize]] in Chemistry for his work on chemiosmosis. 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.
The presence of oxygen and the citric acid cycle allows the pyruvate to be broken down into carbon dioxide and water to produce 24-28 ATP.
 
  
Under certain conditions, protons may be allowed to re-enter the mitochondial matrix without contributing to ATP synthesis. This process, known as ''proton leak'' or ''mitochondrial uncoupling'', results in the unharnessed energy being released as heat. This mechanism for the metabolic generation of heat is employed primarily in specialized tissues, such as the "[[brown fat]]" of newborn or [[hibernation|hibernating]] mammals.
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Under certain conditions, protons may be allowed to re-enter the mitochondrial matrix without contributing to ATP synthesis. This process, known as ''proton leak'' or ''mitochondrial uncoupling'', results in the unharnessed energy being released as heat. This mechanism for the metabolic generation of heat is employed primarily in specialized tissues, such as the "brown fat" of newborn or [[hibernation|hibernating]] mammals.
 +
 
 +
The presence of oxygen and the citric acid cycle allows the pyruvate to be broken down into [[carbon dioxide]] and [[water]] to produce 24-28 ATP.
  
 
==Reproduction and gene inheritance==
 
==Reproduction 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 [[proteins]] and [[polyribosomes]] needed for their synthesis.
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Mitochondria replicate their [[DNA]] and divide mainly in response to the ''energy'' needs of the cell&mdash;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 become inactive or are destroyed. During cell division, mitochondria are distributed to the daughter cells more or less randomly during the division of the [[cytoplasm]].  
  
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]]. However, all of the mitochondria, and therefore all the mitochondrial genes, are contributed to the zygote by the egg. At fertilization of an egg, a single sperm enters the egg along with the mitochondria that it uses to provide the energy needed for its swimming behavior. However, the mitochondria provided by the sperm are targeted for destruction very soon after entry into the egg. The egg itself contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. This type of inheritance is called [[maternal inheritance]] and is common to the mitochondria of all animals. Because mitochondria are inherited from the mother only, the sequence of [[mitochondrial DNA]] is sometimes used to trace the lineage of families.
+
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 [[proteins]] and polyribosomes needed for their synthesis.
  
==Use in population genetic studies==
+
Mitochondrial genes are not inherited by the same mechanism as nuclear genes. At fertilization of an egg by a sperm, the [[egg (biology)|egg]] nucleus and [[sperm]] nucleus each contributes equally to the genetic makeup of the [[zygote]] nucleus. However, all of the mitochondria, and therefore all the mitochondrial genes, are contributed by the egg. At fertilization of an egg, a single sperm enters the egg along with the mitochondria that it uses to provide the energy needed for its swimming behavior. However, the mitochondria provided by the sperm are targeted for destruction very soon after entry into the egg. The egg itself contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. This type of inheritance is called ''maternal inheritance'' and is common to the mitochondria of all [[animal]]s.
''Main article: [[mitochondrial genetics]]''
 
  
Because [[Ovum]] destroys the mitochondria of the [[sperm]] that [[fertilization|fertilize]] them, the [[mitochondrial DNA]] of an individual derives almost exclusively from the mother. That is to say 99.9% comes from the mother. Individuals inherit the other kinds of genes and DNA from both parents jointly. Because of the unique matrilineal transmission of mitochondrial DNA, scientists in [[population genetics]] and [[evolutionary biology]] often use data from mitochondrial DNA sequences to draw conclusions.
+
Because mitochondria are inherited from the mother only, the sequence of mitochondrial DNA is sometimes used to trace the lineage of families.  
  
In 1987 Rebecca Cann of the University of Hawaii compared mitochondrial DNA sampled from women whose ancestors came from different part of the world. The study team compared the differences between the mitochondrial DNA of all the sampled individuals. In this way they created a family tree connecting them. They used statistical techniques to find a root common to all the women. Africa was determined to be the most likely root of human ancestry.
+
In 1987, Rebecca Cann of the University of Hawaii compared mitochondrial DNA sampled from women whose ancestors came from different parts of the world. The study team compared the differences between the mitochondrial DNA of all the sampled individuals. In this way, they created a family tree connecting them. They used statistical techniques to find a root common to all the women. [[Africa]] was determined to be the most likely root of [[human being|human]] ancestry.
  
If the rate of mutation over time could be estimated, they suggested that an approximate date that humans first left Africa could be made. They concluded tahat our human ancestors left Africa between 180,000 and 230,000 years ago.
+
If the rate of mutation over time could be estimated, they suggested that an approximate date that humans first left Africa could be made. They hypothesized that our human ancestors left Africa between 180,000 and 230,000 years ago.
  
 
==Origin==
 
==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 [[endosymbiosis|endosymbiotic]] prokaryotes. Studies of mitochondrial DNA, which is circular and employs a variant [[genetic code]], show their ancestor was a member of the [[Proteobacteria]] [Futuyma 2005].  In particular, the pre-mitochondrion was probably related to the [[Rickettsiales|rickettsia]]s. 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.
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As mitochondria contain [[ribosome]]s and [[DNA]], and are only formed by the division of other mitochondria, it is generally accepted that they were originally derived from [[symbiosis|endosymbiotic]] [[prokaryote]]s. Studies of mitochondrial DNA, which is circular and employs a variant [[genetic code]], suggest their ancestor was a member of the Proteobacteria (Futuyma 2005), and probably related to the Rickettsiales.  
 +
 
 +
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 happened at least 2000 million 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 [[Polyadenylation|polyadenylated]] to yield mature mRNAs. Unlike their nuclear cousins, mitochondrial genes are small, generally lacking [[introns]], and the chromosomes are circular, conforming to the bacterial pattern.
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This happened at least two 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 that are cleaved and polyadenylated to yield mature mRNAs. Unlike their nuclear cousins, mitochondrial genes are small, generally lacking introns (sections of DNA that will be spliced out after transcription, but before the RNA is used), and the chromosomes are circular, conforming to the bacterial pattern.
  
A few groups of unicellular eukaryotes lack mitochondria: the symbiotic [[microsporidia]]ns, [[metamonad]]s, and [[entamoebid]]s, and the free-living [[pelobiont]]s. On [[rRNA]] trees these groups appeared as the most primitive eukaryotes, suggesting they appeared before the origin of mitochondrion, 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. Thus it appears that there are no primitively amitochondriate eukaryotes, and so the origin of mitochondria may have played a critical part in the development of eukaryotic cells.
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A few groups of unicellular [[eukaryote]]s lack mitochondria: the symbiotic microsporidians, metamonads, and entamoebids, and the free-living pelobionts. While this may suggest that these groups are the most primitive eukaryotes, appearing before the origin of mitochondria, it is now generally held to be an artifact&mdash;that they are descendants of eukaryotes with mitochondria and retain genes or organelles derived from mitochondria. Thus, it appears that there are no primitively amitochondriate eukaryotes, and so the origin of mitochondria may have played a critical part in the development of eukaryotic cells.
  
 
==References ==
 
==References ==
* Futuyma, D. J. (2005). "On Darwin's Shoulders". Natural History 114 (9): 64–68.
+
* Alberts, B. et al. 1994. ''Molecular Biology of the Cell'', 3rd Edition. New York: Garland Publishing Inc.
*Scheffler, I.E. (2001). "A century of mitochondrial research: achievements and perspectives". Mitochondrion 1 (1): 3–31.
+
* Cann, R. L., M. Stoneking, and A. C. Wilson. 1987. “Mitochondrial DNA and human evolution.” ''Nature'' 325: 31-36.
*Alberts, B. et.al. (1994). Molecular Biology of the Cell, Third Edition, New York: Garland Publishing Inc..
+
* Futuyma, D. J. 2005. “On Darwin's Shoulders.” ''Natural History'' 114(9):64–68.  
*Cell Biology Graduate Program of the University of Texas Medical Branch:
+
* Margulis L. and D. Sagan. 1986. ''Microcosmos''. New York: Summit Books.
http://cellbio.utmb.edu/cellbio/mitochondria_1.htm#glycolysis
+
* Scheffler, I. E. 2001. “A century of mitochondrial research: Achievements and perspectives.” ''Mitochondrion'' 1(1):3–31.  
*Cann, Stoneking and Wilson, Nature325 (1987): 31-36.
 
{{NCBI-scienceprimer}}
 
 
 
==External links==
 
* [http://www.wadsworth.org/databank/electron/cryomito_dis2.html Video Clip of Rat-liver Mitochondrion from Cryo-electron Tomography]
 
* [http://www.sci.sdsu.edu/TFrey/MitoMovie.htm Mitochondrion Reconstructed by Electron Tomography]
 
* [http://www.the-elso-gazette.org/magazines/issue11/mreviews/mreviews1.asp Review of evidence addressing whether mitochondria form cellular networks or exist as discrete organelles]
 
* [http://www.cytochemistry.net/Cell-biology/mitoch1.htm Mitochondria: Architecture dictates function]
 
* [http://www.zytologie-online.net/mitochondrium.php Mitochondrion with Cell Biology]
 
* [http://www.uni-mainz.de/FB/Medizin/Anatomie/workshop/EM/EMMitoE.html Mitochondra Atlas]
 
* [http://bama.ua.edu/~hsmithso/class/bsc_495/mito-plastids/mito_web.html Other links]
 
 
 
 
 
  
 
{{NCBI-scienceprimer}}
 
{{NCBI-scienceprimer}}
 
 
  
 
{{credit|45384311}}
 
{{credit|45384311}}
 
[[Category:Life sciences]]
 
[[Category:Life sciences]]
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[[Category:Cell biology]]

Latest revision as of 14:49, 29 August 2008


A mitochondrion (plural mitochondria) is an organelle found in most eukaryotic cells. Mitochondria are sometimes described as "cellular power plants," because their primary function is to 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 percent of the cell's cytoplasm. The name comes from the Greek mitos, meaning "thread" and khondrion, meaning "granule."

Mitochondria have their own DNA, and, according to the generally accepted endosymbiotic theory, they were originally derived from external organisms. This theory, which was popularized by Lynn Margulis, fits her view that "Life did not take over the globe by combat, but by networking" (Margulis and Sagan 1986)—in other words, by cooperation rather than Darwinian competition.

Mitochondrion structure

A mitochondrion comprises outer and inner membranes composed of phospholipid bilayers studded with proteins, much like a typical cell membrane. The two membranes, however, have very different properties.

The outer mitochondrial membrane, which encloses the entire organelle, comprises by weight about 50 percent phospholipids forming the membranous structure within which float a variety of enzymes involved in such diverse activities as the elongation of fatty acids, oxidation of epinephrine (adrenaline), and the degradation of tryptophan (an essential amino acid). Also floating in the membrane are numerous integral proteins called porins whose relatively large internal channel (about 2-3 nanometers) is permeable to all molecules of 5,000 daltons (a unit of atomic mass) or less (Alberts 1994). Larger molecules can only transverse the outer membrane by active transport (transport aided by a protein and requiring the input of chemical energy).

Unlike the relatively smoothly curved outer membrane, the inner membrane is recursively invaginated, compacting a large membrane surface area into a small volume. In addition to the essential phospholipid foundation needed for forming a biological membrane, the inner membrane also comprises proteins with three types of functions (Alberts 1994):

  1. Carrying out the oxidation reactions of the respiratory chain.
  2. Making ATP in the matrix.
  3. Transporting proteins that regulate the passage of metabolites (intermediates and products of metabolism) into and out of the matrix.

The inner membrane comprises more than one hundred different polypeptides and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about one protein per 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.

Mitochondria structure :
1) Inner membrane
2) Outer membrane
3) Crista (internal compartments)
4) Matrix

The mitochondrial matrix

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, transfer RNA (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 (Alberts 1994).

Thus, mitochondria possess their own genetic material, and the machinery to manufacture their own RNAs and proteins. 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.

Mitochondrial functions

The primary function of mitochondria is to convert organic materials into cellular energy in the form of ATP. Notably, the inner mitochondrial membrane is folded into numerous cristae (see diagram above), 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 that have greater demand for ATP, such as muscle cells, contain even more cristae than typical liver mitochondria.

Mitochondria play an important role in other metabolic tasks:

  • Apoptosis (programmed cell death)
  • Glutamate-mediated excitotoxic neuronal injury
  • Cellular proliferation
  • Regulation of the cellular redox state (chemical process in which the oxidation number of atoms is changed)
  • Heme synthesis
  • Steroid synthesis
  • Heat production (enabling the organism to stay warm).

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 a variety of mitochondrial diseases.

Energy conversion

Main article: Citric acid cycle

As stated above, the primary function of the mitochondria is the production of ATP. Outside the mitochondria, cells can generate ATP in the absence of oxygen; this process is called glycolysis. Through glycolysis, one molecule of glucose is converted to pyruvate, producing four ATP. Inside the mitochondria, however, much more energy is extracted. This is done by metabolizing the major products of glycolysis: pyruvate and NADH (an important coenzyme, the reduced form of nicotinamide adenine dinucleotide). This metabolism can be performed in two very different ways, depending on the type of cell and the presence or absence of oxygen.

Inside the matrix, the citric acid cycle takes place. The citric acid cycle does not use oxygen. Each pyruvate molecule produced by glycolysis is actively transported across the inner mitochondrial membrane, and into the matrix where it is combined with coenzyme A to form acetyl CoA. Once formed, acetyl CoA is fed into the citric acid cycle , also known as the tricarboxylic acid (TCA) cycle or Krebs cycle. This process creates 3 molecules of NADH and 1 molecule of FADH2, which go on to participate in the next stage, oxidative phosphorylation, which involves oxygen.

The energy from NADH and FADH2 is transferred to oxygen (O2) in several steps via the electron transfer chain. The protein complexes in the inner membrane (NADH dehydrogenase, cytochrome c reductase, cytochrome c oxidase) that perform the transfer use the released energy to pump protons (H+) against a gradient (the concentration of protons in the intermembrane space is higher than that in the matrix).

As the proton concentration increases in the intermembrane space, a strong concentration gradient is built up. The main exit for these protons is through the ATP synthase complex. By transporting protons from the intermembrane space back into the matrix, the ATP synthase complex can make ATP from ADP and inorganic phosphate (Pi). This process is called chemiosmosis and is an example of facilitated diffusion. Peter Mitchell was awarded the 1978 Nobel Prize in Chemistry for his work on chemiosmosis. 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.

Under certain conditions, protons may be allowed to re-enter the mitochondrial matrix without contributing to ATP synthesis. This process, known as proton leak or mitochondrial uncoupling, results in the unharnessed energy being released as heat. This mechanism for the metabolic generation of heat is employed primarily in specialized tissues, such as the "brown fat" of newborn or hibernating mammals.

The presence of oxygen and the citric acid cycle allows the pyruvate to be broken down into carbon dioxide and water to produce 24-28 ATP.

Reproduction and gene inheritance

Mitochondria replicate their DNA and divide mainly in response to the energy needs of the cell—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 become inactive or are destroyed. During 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 proteins and polyribosomes 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 contributes equally to the genetic makeup of the zygote nucleus. However, all of the mitochondria, and therefore all the mitochondrial genes, are contributed by the egg. At fertilization of an egg, a single sperm enters the egg along with the mitochondria that it uses to provide the energy needed for its swimming behavior. However, the mitochondria provided by the sperm are targeted for destruction very soon after entry into the egg. The egg itself contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. This type of inheritance is called maternal inheritance and is common to the mitochondria of all animals.

Because mitochondria are inherited from the mother only, the sequence of mitochondrial DNA is sometimes used to trace the lineage of families.

In 1987, Rebecca Cann of the University of Hawaii compared mitochondrial DNA sampled from women whose ancestors came from different parts of the world. The study team compared the differences between the mitochondrial DNA of all the sampled individuals. In this way, they created a family tree connecting them. They used statistical techniques to find a root common to all the women. Africa was determined to be the most likely root of human ancestry.

If the rate of mutation over time could be estimated, they suggested that an approximate date that humans first left Africa could be made. They hypothesized that our human ancestors left Africa between 180,000 and 230,000 years ago.

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 circular and employs a variant genetic code, suggest their ancestor was a member of the Proteobacteria (Futuyma 2005), and probably related to the Rickettsiales.

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 happened at least two 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 that are cleaved and polyadenylated to yield mature mRNAs. Unlike their nuclear cousins, mitochondrial genes are small, generally lacking introns (sections of DNA that will be spliced out after transcription, but before the RNA is used), and the chromosomes are circular, conforming to the bacterial pattern.

A few groups of unicellular eukaryotes lack mitochondria: the symbiotic microsporidians, metamonads, and entamoebids, and the free-living pelobionts. While this may suggest that these groups are the most primitive eukaryotes, appearing before the origin of mitochondria, it is now generally held to be an artifact—that they are descendants of eukaryotes with mitochondria and retain genes or organelles derived from mitochondria. Thus, it appears that there are no primitively amitochondriate eukaryotes, and so the origin of mitochondria may have played a critical part in the development of eukaryotic cells.

References
ISBN links support NWE through referral fees

  • Alberts, B. et al. 1994. Molecular Biology of the Cell, 3rd Edition. New York: Garland Publishing Inc.
  • Cann, R. L., M. Stoneking, and A. C. Wilson. 1987. “Mitochondrial DNA and human evolution.” Nature 325: 31-36.
  • Futuyma, D. J. 2005. “On Darwin's Shoulders.” Natural History 114(9):64–68.
  • Margulis L. and D. Sagan. 1986. Microcosmos. New York: Summit Books.
  • Scheffler, I. E. 2001. “A century of mitochondrial research: Achievements and perspectives.” Mitochondrion 1(1):3–31.

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