Editing Mitochondrion (section)

== Structure ==
Mitochondria may have a number of different shapes.<ref name="British Society for Cell Biology">{{cite web|title=Mitochondrion – much more than an energy converter|url=http://www.bscb.org/?url=softcell/mito|publisher=British Society for Cell Biology|access-date=August 19, 2013|archive-date=April 4, 2019|archive-url=https://web.archive.org/web/20190404173821/https://bscb.org/?url=softcell%2Fmito|url-status=live}}</ref> A mitochondrion contains outer and inner membranes composed of [[phospholipid bilayer]]s and [[protein]]s.<ref name="Alberts-2005" /> The two membranes have different properties. Because of this double-membraned organization, there are five distinct parts to a mitochondrion:
# The outer mitochondrial membrane,
# The intermembrane space (the space between the outer and inner membranes),
# The inner mitochondrial membrane,
# The [[crista]]e space (formed by infoldings of the inner membrane), and
# The [[mitochondrial matrix|matrix]] (space within the inner membrane), which is a fluid.
Mitochondria have folding to increase surface area, which in turn increases ATP (adenosine triphosphate) production.
Mitochondria stripped of their outer membrane are called [[mitoplast]]s.

===Outer membrane===
The '''outer mitochondrial membrane''', which encloses the entire organelle, is 60 to 75 [[angstrom]]s (Å) thick. It has a protein-to-phospholipid ratio similar to that of the [[cell membrane]] (about 1:1 by weight). It contains large numbers of [[integral membrane protein]]s called [[porin (protein)|porins]]. A major trafficking protein is the pore-forming [[voltage-dependent anion channel]] (VDAC). The [[Voltage-dependent anion channel#Biological function|VDAC]] is the primary transporter of [[nucleotide]]s, [[ion]]s and [[metabolite]]s between the [[cytosol]] and the intermembrane space.<ref name="Blachly-Dyson-2001">{{cite journal | vauthors = Blachly-Dyson E, Forte M | title = VDAC channels | journal = IUBMB Life | volume = 52 | issue = 3–5 | pages = 113–118 | date = September 2001 | pmid = 11798022 | doi = 10.1080/15216540152845902 | doi-access = free }}</ref><ref name="Hoogenboom-2007">{{cite journal | vauthors = Hoogenboom BW, Suda K, Engel A, Fotiadis D | title = The supramolecular assemblies of voltage-dependent anion channels in the native membrane | journal = Journal of Molecular Biology | volume = 370 | issue = 2 | pages = 246–255 | date = July 2007 | pmid = 17524423 | doi = 10.1016/j.jmb.2007.04.073 }}</ref> It is formed as a [[beta barrel]] that spans the outer membrane, similar to that in the [[gram-negative]] [[bacterial outer membrane]].<ref name="Zeth-2010">{{cite journal | vauthors = Zeth K | title = Structure and evolution of mitochondrial outer membrane proteins of beta-barrel topology | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1797 | issue = 6–7 | pages = 1292–1299 | date = June 2010 | pmid = 20450883 | doi = 10.1016/j.bbabio.2010.04.019 | doi-access = free }}</ref> Larger proteins can enter the mitochondrion if a signaling sequence at their [[N-terminus]] binds to a large multisubunit [[Mitochondrial membrane transport protein|protein]] called [[Translocase of the outer membrane|translocase in the outer membrane]], which then [[active transport|actively moves]] them across the membrane.<ref name="Herrmann-2000">{{cite journal | vauthors = Herrmann JM, Neupert W | title = Protein transport into mitochondria | journal = Current Opinion in Microbiology | volume = 3 | issue = 2 | pages = 210–214 | date = April 2000 | pmid = 10744987 | doi = 10.1016/S1369-5274(00)00077-1 | url = http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-7488-5 }}</ref> Mitochondrial [[protein precursor|pro-proteins]] are imported through specialised translocation complexes.

The outer membrane also contains [[enzyme]]s involved in such diverse activities as the elongation of [[fatty acid]]s, [[oxidation]] of [[epinephrine]], and the [[Biodegradation|degradation]] of [[tryptophan]]. These enzymes include [[monoamine oxidase]], [[rotenone]]-insensitive NADH-cytochrome c-reductase, [[kynurenine]] [[hydroxylase]] and fatty acid Co-A [[ligase]]. Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to cell death.<ref name="Chipuk-2006">{{cite journal | vauthors = Chipuk JE, Bouchier-Hayes L, Green DR | title = Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario | journal = Cell Death and Differentiation | volume = 13 | issue = 8 | pages = 1396–1402 | date = August 2006 | pmid = 16710362 | doi = 10.1038/sj.cdd.4401963 | doi-access = free }}</ref> The outer mitochondrial membrane can associate with the endoplasmic reticulum (ER) membrane, in a structure called MAM (mitochondria-associated ER-membrane). This is important in the ER-mitochondria calcium signaling and is involved in the transfer of lipids between the ER and mitochondria.<ref name="Hayashi-2009"/> Outside the outer membrane are small (diameter: 60 Å) particles named sub-units of Parson.

===Intermembrane space===
The '''mitochondrial intermembrane space''' is the space between the outer membrane and the inner membrane. It is also known as perimitochondrial space. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules, such as ions and sugars, in the intermembrane space is the same as in the [[cytosol]].<ref name="Alberts-2005"/> However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the [[cytosol]]. One [[protein]] that is localized to the intermembrane space in this way is [[cytochrome c]].<ref name="Chipuk-2006"/>

===Inner membrane===
{{Main|Inner mitochondrial membrane}}

The inner mitochondrial membrane contains proteins with three types of functions:<ref name="Alberts-2005"/>
# Those that perform the [[electron transport chain]] [[redox]] reactions
# [[ATP synthase]], which generates [[Adenosine triphosphate|ATP]] in the matrix
# Specific [[membrane transport protein|transport proteins]] that regulate [[metabolite]] passage into and out of the [[mitochondrial matrix]]

It contains more than 151 different [[polypeptide]]s, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1&nbsp;protein for 15&nbsp;phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion.<ref name="Schenkel-2014">{{cite journal | vauthors = Schenkel LC, Bakovic M | title = Formation and regulation of mitochondrial membranes | journal = International Journal of Cell Biology | volume = 2014 | pages = 709828 | date = January 2014 | pmid = 24578708 | pmc = 3918842 | doi = 10.1155/2014/709828 | doi-access = free }}</ref> Additionally, the inner membrane is rich in an unusual phospholipid, [[cardiolipin]]. This phospholipid was originally discovered in [[Bos taurus|cow]] hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes.<ref name="McMillin-2002">{{cite journal | vauthors = McMillin JB, Dowhan W | title = Cardiolipin and apoptosis | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1585 | issue = 2–3 | pages = 97–107 | date = December 2002 | pmid = 12531542 | doi = 10.1016/S1388-1981(02)00329-3 }}</ref> Cardiolipin contains four fatty acids rather than two, and may help to make the inner membrane impermeable,<ref name="Alberts-2005"/> and its disruption can lead to multiple clinical disorders including neurological disorders and cancer.<ref>{{cite journal | vauthors = Bautista JS, Falabella M, Flannery PJ, Hanna MG, Heales SJ, Pope SA, Pitceathly RD | title = Advances in methods to analyse cardiolipin and their clinical applications | journal = Trends in Analytical Chemistry | volume = 157 | pages = 116808 | date = December 2022 | pmid = 36751553 | pmc = 7614147 | doi = 10.1016/j.trac.2022.116808 }}</ref> Unlike the outer membrane, the inner membrane does not contain porins, and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the [[translocase of the inner membrane]] (TIM) complex or via [[OXA1L]].<ref name="Herrmann-2000"/> In addition, there is a membrane potential across the inner membrane, formed by the action of the [[enzyme]]s of the [[electron transport chain]]. Inner membrane [[mitochondrial fusion|fusion]] is mediated by the inner membrane protein [[OPA1]].<ref name="Youle-2012">{{cite journal | vauthors = Youle RJ, van der Bliek AM | title = Mitochondrial fission, fusion, and stress | journal = Science | volume = 337 | issue = 6098 | pages = 1062–1065 | date = August 2012 | pmid = 22936770 | pmc = 4762028 | doi = 10.1126/science.1219855 | bibcode = 2012Sci...337.1062Y }}</ref>

====Cristae====
[[File:MitochondrionCAM.jpg|thumb|250 px|right|Cross-sectional image of cristae in a [[rat]] liver mitochondrion to demonstrate the likely 3D structure and relationship to the inner membrane]]
{{Main|Crista}}

The inner mitochondrial membrane is compartmentalized into numerous folds called [[crista]]e, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. For typical liver mitochondria, the area of the inner membrane is about five times as large as that of the outer membrane. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. Mitochondria within the same cell can have substantially different crista-density, with the ones that are required to produce more energy having much more crista-membrane surface.<ref name="Cserép-2018">{{cite journal | vauthors = Cserép C, Pósfai B, Schwarcz AD, Dénes Á | title = Mitochondrial Ultrastructure Is Coupled to Synaptic Performance at Axonal Release Sites | journal = eNeuro | volume = 5 | issue = 1 | pages = ENEURO.0390–17.2018 | date = 2018 | pmid = 29383328 | pmc = 5788698 | doi = 10.1523/ENEURO.0390-17.2018 }}</ref> These folds are studded with small round bodies known as [[F-ATPase|F{{sub|1}} particles]] or oxysomes.<ref name="Mannella-2006">{{cite journal | vauthors = Mannella CA | title = Structure and dynamics of the mitochondrial inner membrane cristae | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1763 | issue = 5–6 | pages = 542–548 | year = 2006 | pmid = 16730811 | doi = 10.1016/j.bbamcr.2006.04.006 | doi-access =  }}</ref>

===Matrix===
{{Main|Mitochondrial matrix}}
The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total proteins in a mitochondrion.<ref name="Alberts-2005"/> The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly concentrated mixture of hundreds of enzymes, 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]].<ref name="Alberts-2005" /> The DNA molecules are packaged into nucleoids by proteins, one of which is [[TFAM]].<ref>{{cite journal | vauthors = Bogenhagen DF | title = Mitochondrial DNA nucleoid structure | journal = Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | volume = 1819 | issue = 9–10 | pages = 914–920 | date = September 2012 | pmid = 22142616 | doi = 10.1016/j.bbagrm.2011.11.005 }}</ref>