Editing Mitochondrion (section)

== Function ==
The most prominent roles of mitochondria are to produce the energy currency of the cell, [[Adenosine triphosphate|ATP]] (i.e., phosphorylation of [[Adenosine diphosphate|ADP]]), through respiration and to regulate cellular [[metabolism]].<ref name="Voet-2006"/> The central set of reactions involved in ATP production are collectively known as the [[citric acid cycle]], or the [[Hans Adolf Krebs|Krebs]] cycle, and [[oxidative phosphorylation]]. However, the mitochondrion has many other functions in addition to the production of ATP.

===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 oxidizing the major products of [[glucose]]: [[pyruvate]], and [[NADH]], which are produced in the cytosol.<ref name="Voet-2006"/> This type of [[cellular respiration]], known as [[aerobic respiration]], is dependent on the presence of [[oxygen]]. When oxygen is limited, the glycolytic products will be metabolized by [[Fermentation (biochemistry)|anaerobic fermentation]], a process that is independent of the mitochondria.<ref name="Voet-2006"/> The production of ATP from glucose and oxygen has an approximately 13-times higher yield during aerobic respiration compared to fermentation.<ref>{{cite journal | vauthors = Rich PR | title = The molecular machinery of Keilin's respiratory chain | journal = Biochemical Society Transactions | volume = 31 | issue = Pt 6 | pages = 1095–1105 | date = December 2003 | pmid = 14641005 | doi = 10.1042/BST0311095 }}</ref> Plant mitochondria can also produce a limited amount of ATP either by breaking the sugar produced during photosynthesis or without oxygen by using the alternate substrate [[nitrite]].<ref name="Stoimenova-2007">{{cite journal | vauthors = Stoimenova M, Igamberdiev AU, Gupta KJ, Hill RD | title = Nitrite-driven anaerobic ATP synthesis in barley and rice root mitochondria | journal = Planta | volume = 226 | issue = 2 | pages = 465–474 | date = July 2007 | pmid = 17333252 | doi = 10.1007/s00425-007-0496-0 | bibcode = 2007Plant.226..465S }}</ref> ATP crosses out through the inner membrane with the help of a [[ATP–ADP translocase|specific protein]], and across the outer membrane via [[Porin (protein)|porins]].<ref name="Neupert-1997">{{cite journal | vauthors = Neupert W | title = Protein import into mitochondria | journal = Annual Review of Biochemistry | volume = 66 | pages = 863–917 | year = 1997 | pmid = 9242927 | doi = 10.1146/annurev.biochem.66.1.863 }}</ref> After conversion of ATP to [[Adenosine diphosphate|ADP]] by [[dephosphorylation]] that releases energy, ADP returns via the same route.

====Pyruvate and the citric acid cycle====
{{Main|Citric acid cycle}}

[[Pyruvate]] molecules produced by [[glycolysis]] are [[active transport|actively transported]] across the inner mitochondrial membrane, and into the matrix where they can either be [[Redox|oxidized]] and combined with [[coenzyme A]] to form CO{{sub|2}}, [[acetyl-CoA]], and [[NADH]],<ref name="Voet-2006" /> or they can be [[carboxylated]] (by [[pyruvate carboxylase]]) to form oxaloacetate. This latter reaction "fills up" the amount of oxaloacetate in the citric acid cycle and is therefore an [[anaplerotic reaction]], increasing the cycle's capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g., in [[striated muscle tissue|muscle]]) are suddenly increased by activity.<ref name="Stryer-1995">{{cite book | vauthors = Stryer L | title=In: Biochemistry. |chapter= Citric acid cycle. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 509–527, 569–579, 614–616, 638–641, 732–735, 739–748, 770–773 |isbn= 0716720094 }}</ref>

In the citric acid cycle, all the intermediates (e.g. [[citrate]], [[Isocitric acid|iso-citrate]], [[Alpha-Ketoglutaric acid|alpha-ketoglutarate]], succinate, [[Fumaric acid|fumarate]], [[Malic acid|malate]] and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that the additional amount is retained within the cycle, increasing all the other intermediates as one is converted into the other. Hence, the addition of any one of them to the cycle has an [[Anaplerotic reactions|anaplerotic]] effect, and its removal has a cataplerotic effect. These anaplerotic and [[cataplerotic]] reactions will, during the course of the cycle, increase or decrease the amount of oxaloacetate available to combine with acetyl-CoA to form citric acid. This in turn increases or decreases the rate of [[Adenosine triphosphate|ATP]] production by the mitochondrion, and thus the availability of ATP to the cell.<ref name="Stryer-1995" />

Acetyl-CoA, on the other hand, derived from pyruvate oxidation, or from the [[beta-oxidation]] of [[fatty acids]], is the only fuel to enter the citric acid cycle. With each turn of the cycle one molecule of acetyl-CoA is consumed for every molecule of oxaloacetate present in the mitochondrial matrix, and is never regenerated. It is the oxidation of the acetate portion of acetyl-CoA that produces CO{{sub|2}} and water, with the energy thus released captured in the form of ATP.<ref name="Stryer-1995" />

In the liver, the [[carboxylation]] of [[cytosol]]ic pyruvate into intra-mitochondrial oxaloacetate is an early step in the [[gluconeogenesis|gluconeogenic]] pathway, which converts [[lactic acid|lactate]] and de-aminated [[alanine]] into glucose,<ref name="Voet-2006" /><ref name="Stryer-1995" /> under the influence of high levels of [[glucagon]] and/or [[epinephrine]] in the blood.<ref name="Stryer-1995" /> Here, the addition of oxaloacetate to the mitochondrion does not have a net anaplerotic effect, as another citric acid cycle intermediate (malate) is immediately removed from the mitochondrion to be converted to cytosolic oxaloacetate, and ultimately to glucose, in a process that is almost the reverse of [[glycolysis]].<ref name="Stryer-1995" />

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 as part of Complex II.<ref>{{cite journal | vauthors = King A, Selak MA, Gottlieb E | title = Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer | journal = Oncogene | volume = 25 | issue = 34 | pages = 4675–4682 | date = August 2006 | pmid = 16892081 | doi = 10.1038/sj.onc.1209594 | doi-access =  }}</ref> The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of [[NADH]] and one molecule of [[FADH2|FADH{{sub|2}}]]) that are a source of electrons for the [[electron transport chain]], and a molecule of [[Guanosine triphosphate|GTP]] (which is readily converted to an ATP).<ref name="Voet-2006"/>

==== O{{sub|2}} and NADH: energy-releasing reactions ====
{{Main|Oxidative phosphorylation|electron transport chain}}
[[File:Electron transport chain.svg|thumb|400px|Electron transport chain in the mitochondrial intermembrane space]]

The electrons from NADH and FADH{{sub|2}} are transferred to oxygen (O{{sub|2}}) and hydrogen (protons) in several steps via an electron transport chain. NADH and FADH{{sub|2}} molecules are produced within the matrix via the citric acid cycle and in the cytoplasm by [[glycolysis]]. [[Reducing equivalent]]s from the cytoplasm can be imported via the [[malate-aspartate shuttle]] system of [[antiporter]] proteins or fed into the electron transport chain using a [[glycerol phosphate shuttle]].<ref name="Voet-2006"/>

The major energy-releasing reactions<ref name="Voet-2004">{{cite book | vauthors = Voet D, Voet JG |title=Biochemistry |date=2004 |publisher=Wiley |location=New York, NY |isbn=978-0-471-19350-0 |edition=3rd | page = 804 }}</ref><ref name="Atkins-2006">{{cite book | vauthors = Atkins P, de Paula J | date = 2006 | chapter = Impact on biochemistry: Energy conversion in biological cells | title = Physical Chemistry | edition = 8th | pages = 225–229 | publisher = Freeman | location = New York | isbn = 978-0-7167-8759-4 }}</ref> that make the mitochondrion the "powerhouse of the cell" occur at [[Electron transport chain#Mitochondrial redox carriers|protein complexes I, III and IV]] in the inner mitochondrial membrane ([[NADH dehydrogenase (ubiquinone)]], [[Coenzyme Q - cytochrome c reductase|cytochrome c reductase]], and [[cytochrome c oxidase]]). At [[complex IV]], O<sub>2</sub> reacts with the reduced form of iron in [[cytochrome c]]:

:{{chem2 | O2 + 4 H+(aq) + 4 Fe(2+)(cyt c) -> 2 H2O + 4 Fe(3+)(cyt c) }}{{spaces|4}}Δ<sub>r</sub>G<sup>o'</sup> = -218 kJ/mol

releasing a lot of [[Gibbs free energy|free energy]]<ref name="Atkins-2006"/><ref name="Voet-2004"/> from the reactants without breaking bonds of an organic fuel. The free energy put in to remove an electron from Fe<sup>2+</sup> is released at [[complex III]] when Fe<sup>3+</sup> of cytochrome c reacts to oxidize [[ubiquinol]] (QH<sub>2</sub>):

:{{chem2 | 2 Fe(3+)(cyt c) + QH2 -> 2 Fe(2+)(cyt c) + Q + 2 H+(aq) }}{{spaces|4}}Δ<sub>r</sub>G<sup>o'</sup> = -30 kJ/mol

The [[ubiquinone]] (Q) generated reacts, in [[complex I]], with NADH:

:{{chem2 |Q + H+(aq) + NADH -> QH2 + NAD+ }}{{spaces|4}}Δ<sub>r</sub>G<sup>o'</sup> = -81 kJ/mol

While the reactions are controlled by an electron transport chain, free electrons are not amongst the reactants or products in the three reactions shown and therefore do not affect the free energy released, which is used to pump [[Hydrogen ion|protons]] (H{{sup|+}}) into the intermembrane space. This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming [[reactive oxygen species]] such as [[superoxide]].<ref name="Voet-2006" /> This can cause [[oxidative stress]] in the mitochondria and may contribute to the decline in mitochondrial function associated with aging.<ref name="Huang-2004">{{cite journal | vauthors = Huang H, Manton KG | title = The role of oxidative damage in mitochondria during aging: a review | journal = Frontiers in Bioscience | volume = 9 | issue = 1–3 | pages = 1100–1117 | date = May 2004 | pmid = 14977532 | doi = 10.2741/1298 }}</ref>

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 [[Adenosine triphosphate|ATP]] from ADP and inorganic phosphate (P{{sub|i}}).<ref name="Voet-2006"/> This process is called [[chemiosmosis]], and was first described by [[Peter D. Mitchell|Peter Mitchell]],<ref name="Mitchell-1967a">{{cite journal | vauthors = Mitchell P, Moyle J | title = Chemiosmotic hypothesis of oxidative phosphorylation | journal = Nature | volume = 213 | issue = 5072 | pages = 137–139 | date = January 1967 | pmid = 4291593 | doi = 10.1038/213137a0 | bibcode = 1967Natur.213..137M }}</ref><ref name="Mitchell-1967b">{{cite journal | vauthors = Mitchell P | title = Proton current flow in mitochondrial systems | journal = Nature | volume = 214 | issue = 5095 | pages = 1327–1328 | date = June 1967 | pmid = 6056845 | doi = 10.1038/2141327a0 | bibcode = 1967Natur.214.1327M }}</ref> 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.<ref>{{cite web |last =Nobel Foundation |title =Chemistry 1997 |url =http://nobelprize.org/nobel_prizes/chemistry/laureates/1997/ |access-date =December 16, 2007 |archive-date =July 8, 2007 |archive-url =https://web.archive.org/web/20070708165350/http://nobelprize.org/nobel_prizes/chemistry/laureates/1997/ |url-status =live }}</ref>

====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. The process results in the unharnessed potential energy of the proton [[Electrochemistry|electrochemical]] gradient being released as heat.<ref name="Voet-2006"/> The process is mediated by a proton channel called [[thermogenin]], or [[UCP1]].<ref name="Mozo-2005">{{cite journal | vauthors = Mozo J, Emre Y, Bouillaud F, Ricquier D, Criscuolo F | title = Thermoregulation: what role for UCPs in mammals and birds? | journal = Bioscience Reports | volume = 25 | issue = 3–4 | pages = 227–249 | date = November 2005 | pmid = 16283555 | doi = 10.1007/s10540-005-2887-4 }}</ref> Thermogenin is primarily found in [[brown adipose tissue]], or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue is found in mammals, and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age.<ref name="Mozo-2005"/>

=== Mitochondrial fatty acid synthesis ===
{{Main|Mitochondrial fatty acid synthesis}}

Mitochondrial fatty acid synthesis (mtFASII) is essential for cellular respiration and mitochondrial biogenesis.<ref>{{cite journal | vauthors = Kastaniotis AJ, Autio KJ, Kerätär JM, Monteuuis G, Mäkelä AM, Nair RR, Pietikäinen LP, Shvetsova A, Chen Z, Hiltunen JK | title = Mitochondrial fatty acid synthesis, fatty acids and mitochondrial physiology | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1862 | issue = 1 | pages = 39–48 | date = January 2017 | pmid = 27553474 | doi = 10.1016/j.bbalip.2016.08.011 }}</ref> It is also thought to play a role as a mediator in [[Cell signaling|intracellular signaling]] due to its influence on the levels of bioactive lipids, such as [[Lysophospholipase|lysophospholipids]] and [[sphingolipid]]s.<ref>{{cite journal | vauthors = Clay HB, Parl AK, Mitchell SL, Singh L, Bell LN, Murdock DG | title = Altering the Mitochondrial Fatty Acid Synthesis (mtFASII) Pathway Modulates Cellular Metabolic States and Bioactive Lipid Profiles as Revealed by Metabolomic Profiling | journal = PLOS ONE | volume = 11 | issue = 3 | pages = e0151171 | date = March 2016 | pmid = 26963735 | pmc = 4786287 | doi = 10.1371/journal.pone.0151171 | veditors = Peterson J | doi-access = free | bibcode = 2016PLoSO..1151171C }}</ref>

[[Octanoyl-(acyl-carrier protein):protein N-octanoyltransferase|Octanoyl-ACP]] (C8) is considered to be the most important end product of mtFASII, which also forms the starting substrate of [[lipoic acid]] biosynthesis.<ref name="Nowinski-2018">{{cite journal | vauthors = Nowinski SM, Van Vranken JG, Dove KK, Rutter J | title = Impact of Mitochondrial Fatty Acid Synthesis on Mitochondrial Biogenesis | journal = Current Biology | volume = 28 | issue = 20 | pages = R1212–R1219 | date = October 2018 | pmid = 30352195 | pmc = 6258005 | doi = 10.1016/j.cub.2018.08.022 | bibcode = 2018CBio...28R1212N }}</ref> Since lipoic acid is the cofactor of important mitochondrial enzyme complexes, such as the [[pyruvate dehydrogenase complex]] (PDC), [[Oxoglutarate dehydrogenase complex|α-ketoglutarate dehydrogenase complex]] (OGDC), [[Branched-chain alpha-keto acid dehydrogenase complex|branched-chain α-ketoacid dehydrogenase complex]] (BCKDC), and in the [[glycine cleavage system]] (GCS), mtFASII has an influence on energy metabolism.<ref>{{cite journal | vauthors = Wehbe Z, Behringer S, Alatibi K, Watkins D, Rosenblatt D, Spiekerkoetter U, Tucci S | title = The emerging role of the mitochondrial fatty-acid synthase (mtFASII) in the regulation of energy metabolism | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1864 | issue = 11 | pages = 1629–1643 | date = November 2019 | pmid = 31376476 | doi = 10.1016/j.bbalip.2019.07.012 }}</ref>

Other products of mtFASII play a role in the regulation of mitochondrial translation, [[Iron-sulfur cluster biosynthesis|FeS cluster biogenesis]] and assembly of oxidative phosphorylation complexes.<ref name="Nowinski-2018" />

Furthermore, with the help of mtFASII and acylated ACP, acetyl-CoA regulates its consumption in mitochondria.<ref name="Nowinski-2018" />

===Uptake, storage and release of calcium ions===
[[File:Chondrocyte- calcium stain.jpg|right|thumb|400 px|[[Transmission electron microscope|Transmission]] [[Micrograph|electron micrograph]] of a [[chondrocyte]], stained for calcium, showing its nucleus (N) and mitochondria (M)]]
The concentrations of free calcium in the cell can regulate an array of reactions and is important for [[signal transduction]] in the cell. Mitochondria can transiently [[Calcium storage|store calcium]], a contributing process for the cell's homeostasis of calcium.<ref name="Santulli-2015c">{{cite journal | vauthors = Santulli G, Xie W, Reiken SR, Marks AR | title = Mitochondrial calcium overload is a key determinant in heart failure | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 36 | pages = 11389–11394 | date = September 2015 | pmid = 26217001 | pmc = 4568687 | doi = 10.1073/pnas.1513047112 | doi-access = free | bibcode = 2015PNAS..11211389S }}</ref>
<ref name="Siegel-1999">{{cite book | veditors = Siegel GJ, Agranoff BW, Fisher SK, Albers RW, Uhler MD |title=Basic Neurochemistry |edition=6 |year=1999 |isbn=978-0397518203 |publisher=Lippincott Williams & Wilkins }}</ref> Their ability to rapidly take in calcium for later release makes them good "cytosolic buffers" for calcium.<ref name="Rossier-2006"/><ref>{{cite journal | vauthors = Brighton CT, Hunt RM | title = Mitochondrial calcium and its role in calcification. Histochemical localization of calcium in electron micrographs of the epiphyseal growth plate with K-pyroantimonate | journal = Clinical Orthopaedics and Related Research | volume = 100 | issue = 5 | pages = 406–416 | date = May 1974 | pmid = 4134194 | doi = 10.1097/00003086-197405000-00057 }}</ref><ref>
{{cite journal | vauthors = Brighton CT, Hunt RM | title = The role of mitochondria in growth plate calcification as demonstrated in a rachitic model | journal = The Journal of Bone and Joint Surgery. American Volume | volume = 60 | issue = 5 | pages = 630–639 | date = July 1978 | pmid = 681381 | doi = 10.2106/00004623-197860050-00007 }}</ref> The endoplasmic reticulum (ER) is the most significant storage site of calcium,<ref name="Santulli-2015b"/> and there is a significant interplay between the mitochondrion and ER with regard to calcium.<ref>{{cite journal | vauthors = Pizzo P, Pozzan T | title = Mitochondria-endoplasmic reticulum choreography: structure and signaling dynamics | journal = Trends in Cell Biology | volume = 17 | issue = 10 | pages = 511–517 | date = October 2007 | pmid = 17851078 | doi = 10.1016/j.tcb.2007.07.011 }}</ref> The calcium is taken up into the [[mitochondrial matrix|matrix]] by the [[mitochondrial calcium uniporter]] on the [[inner mitochondrial membrane]].<ref name="Miller-1998">{{cite journal | vauthors = Miller RJ | title = Mitochondria - the Kraken wakes! | journal = Trends in Neurosciences | volume = 21 | issue = 3 | pages = 95–97 | date = March 1998 | pmid = 9530913 | doi = 10.1016/S0166-2236(97)01206-X }}</ref> It is primarily driven by the mitochondrial [[membrane potential]].<ref name="Siegel-1999"/> Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-induced-calcium-release" pathways.<ref name="Miller-1998"/> This can initiate calcium spikes or calcium waves with large changes in the membrane potential. These can activate a series of [[second messenger system]] proteins that can coordinate processes such as [[Synaptic vesicle|neurotransmitter release]] in nerve cells and release of [[hormone]]s in endocrine cells.<ref name="Santulli-2015a">{{cite journal | vauthors = Santulli G, Pagano G, Sardu C, Xie W, Reiken S, D'Ascia SL, Cannone M, Marziliano N, Trimarco B, Guise TA, Lacampagne A, Marks AR | title = Calcium release channel RyR2 regulates insulin release and glucose homeostasis | journal = The Journal of Clinical Investigation | volume = 125 | issue = 5 | pages = 1968–1978 | date = May 2015 | pmid = 25844899 | pmc = 4463204 | doi = 10.1172/JCI79273 }}</ref>

Ca{{sup|2+}} influx to the mitochondrial matrix has recently been implicated as a mechanism to regulate respiratory [[bioenergetics]] by allowing the electrochemical potential across the membrane to transiently "pulse" from ΔΨ-dominated to pH-dominated, facilitating a reduction of [[oxidative stress]].<ref>{{cite journal | vauthors = Schwarzländer M, Logan DC, Johnston IG, Jones NS, Meyer AJ, Fricker MD, Sweetlove LJ | title = Pulsing of membrane potential in individual mitochondria: a stress-induced mechanism to regulate respiratory bioenergetics in Arabidopsis | journal = The Plant Cell | volume = 24 | issue = 3 | pages = 1188–1201 | date = March 2012 | pmid = 22395486 | pmc = 3336130 | doi = 10.1105/tpc.112.096438 | bibcode = 2012PlanC..24.1188S }}</ref> In neurons, concomitant increases in cytosolic and mitochondrial calcium act to synchronize neuronal activity with mitochondrial energy metabolism. Mitochondrial matrix calcium levels can reach the tens of micromolar levels, which is necessary for the activation of [[isocitrate dehydrogenase]], one of the key regulatory enzymes of the [[Krebs cycle]].<ref>{{cite journal | vauthors = Ivannikov MV, Macleod GT | title = Mitochondrial free Ca²⁺ levels and their effects on energy metabolism in Drosophila motor nerve terminals | journal = Biophysical Journal | volume = 104 | issue = 11 | pages = 2353–2361 | date = June 2013 | pmid = 23746507 | pmc = 3672877 | doi = 10.1016/j.bpj.2013.03.064 | bibcode = 2013BpJ...104.2353I }}</ref>

===Cellular proliferation regulation===
The relationship between cellular proliferation and mitochondria has been investigated. Tumor cells require ample ATP to synthesize bioactive compounds such as [[lipid]]s, [[protein]]s, and [[nucleotide]]s for rapid proliferation.<ref name="Weinberg-2009">{{cite journal | vauthors = Weinberg F, Chandel NS | title = Mitochondrial metabolism and cancer | journal = Annals of the New York Academy of Sciences | volume = 1177 | issue = 1 | pages = 66–73 | date = October 2009 | pmid = 19845608 | doi = 10.1111/j.1749-6632.2009.05039.x | bibcode = 2009NYASA1177...66W }}</ref> The majority of ATP in tumor cells is generated via the [[oxidative phosphorylation]] pathway (OxPhos).<ref name="Moreno-Sánchez-2007">{{cite journal | vauthors = Moreno-Sánchez R, Rodríguez-Enríquez S, Marín-Hernández A, Saavedra E | title = Energy metabolism in tumor cells | journal = The FEBS Journal | volume = 274 | issue = 6 | pages = 1393–1418 | date = March 2007 | pmid = 17302740 | doi = 10.1111/j.1742-4658.2007.05686.x }}</ref> Interference with OxPhos cause [[cell cycle]] arrest suggesting that mitochondria play a role in cell proliferation.<ref name="Moreno-Sánchez-2007"/> Mitochondrial ATP production is also vital for [[cell division]] and differentiation in infection<ref>{{cite journal | vauthors = Mistry JJ, Marlein CR, Moore JA, Hellmich C, Wojtowicz EE, Smith JG, Macaulay I, Sun Y, Morfakis A, Patterson A, Horton RH, Divekar D, Morris CJ, Haestier A, Di Palma F, Beraza N, Bowles KM, Rushworth SA | title = ROS-mediated PI3K activation drives mitochondrial transfer from stromal cells to hematopoietic stem cells in response to infection | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 49 | pages = 24610–24619 | date = December 2019 | pmid = 31727843 | pmc = 6900710 | doi = 10.1073/pnas.1913278116 | doi-access = free | bibcode = 2019PNAS..11624610M }}</ref> in addition to basic functions in the cell including the regulation of cell volume, solute [[concentration]], and cellular architecture.<ref name="Pedersen-1994">{{cite journal | vauthors = Pedersen PL | title = ATP synthase. The machine that makes ATP | journal = Current Biology | volume = 4 | issue = 12 | pages = 1138–1141 | date = December 1994 | pmid = 7704582 | doi = 10.1016/S0960-9822(00)00257-8 | bibcode = 1994CBio....4.1138P }}</ref><ref name="Pattappa-2011">{{cite journal | vauthors = Pattappa G, Heywood HK, de Bruijn JD, Lee DA | title = The metabolism of human mesenchymal stem cells during proliferation and differentiation | journal = Journal of Cellular Physiology | volume = 226 | issue = 10 | pages = 2562–2570 | date = October 2011 | pmid = 21792913 | doi = 10.1002/jcp.22605 }}</ref><ref name="Agarwal-2011">{{cite journal | vauthors = Agarwal B | title = A role for anions in ATP synthesis and its molecular mechanistic interpretation | journal = Journal of Bioenergetics and Biomembranes | volume = 43 | issue = 3 | pages = 299–310 | date = June 2011 | pmid = 21647635 | doi = 10.1007/s10863-011-9358-3 }}</ref> ATP levels differ at various stages of the cell cycle suggesting that there is a relationship between the abundance of ATP and the cell's ability to enter a new cell cycle.<ref name="Sweet-1999">{{cite journal | vauthors = Sweet S, Singh G | title = Changes in mitochondrial mass, membrane potential, and cellular adenosine triphosphate content during the cell cycle of human leukemic (HL-60) cells | journal = Journal of Cellular Physiology | volume = 180 | issue = 1 | pages = 91–96 | date = July 1999 | pmid = 10362021 | doi = 10.1002/(SICI)1097-4652(199907)180:1<91::AID-JCP10>3.0.CO;2-6 }}</ref> ATP's role in the basic functions of the cell make the [[cell cycle]] sensitive to changes in the availability of mitochondrial derived ATP.<ref name="Sweet-1999"/> The variation in ATP levels at different stages of the cell cycle support the hypothesis that mitochondria play an important role in cell cycle regulation.<ref name="Sweet-1999"/> Although the specific mechanisms between mitochondria and the cell cycle regulation is not well understood, studies have shown that low energy cell cycle checkpoints monitor the energy capability before committing to another round of cell division.<ref name="McBride-2006"/>

=== Programmed cell death and innate immunity ===
{{Further|Programmed cell death#Intrinsic Pathway}}

[[Programmed cell death]] (PCD) is crucial for various physiological functions, including organ development and cellular homeostasis. It serves as an intrinsic mechanism to prevent [[malignant transformation]] and plays a fundamental role in [[Immune system|immunity]] by aiding in antiviral defense, pathogen elimination, inflammation, and immune cell recruitment.<ref>{{cite journal | vauthors = Riera Romo M | title = Cell death as part of innate immunity: Cause or consequence? | journal = Immunology | volume = 163 | issue = 4 | pages = 399–415 | date = August 2021 | pmid = 33682112 | pmc = 8274179 | doi = 10.1111/imm.13325 }}</ref>

Mitochondria have long been recognized for their central role in the [[Apoptosis#Intrinsic pathway|intrinsic pathway]] of [[apoptosis]], a form of PCD.<ref>{{cite journal | vauthors = Green DR | title = Apoptotic pathways: the roads to ruin | journal = Cell | volume = 94 | issue = 6 | pages = 695–698 | date = September 1998 | pmid = 9753316 | doi = 10.1016/S0092-8674(00)81728-6 | doi-access = free }}</ref> In recent decades, they have also been identified as a signalling hub for much of the [[innate immune system]].<ref name="Bahat-2021">{{cite journal | vauthors = Bahat A, MacVicar T, Langer T | title = Metabolism and Innate Immunity Meet at the Mitochondria | language = English | journal = Frontiers in Cell and Developmental Biology | volume = 9 | pages = 720490 | date = 2021-07-27 | pmid = 34386501 | doi = 10.3389/fcell.2021.720490 | doi-access = free | pmc = 8353256 }}</ref> The [[Symbiogenesis|endosymbiotic origin]] of mitochondria distinguishes them from other cellular components, and the exposure of mitochondrial elements to the [[cytosol]] can trigger the same pathways as infection markers. These pathways lead to [[apoptosis]], [[autophagy]], or the induction of proinflammatory genes.<ref name="Murphy-2024">{{cite journal | vauthors = Murphy MP, O'Neill LA | title = A break in mitochondrial endosymbiosis as a basis for inflammatory diseases | journal = Nature | volume = 626 | issue = 7998 | pages = 271–279 | date = February 2024 | pmid = 38326590 | doi = 10.1038/s41586-023-06866-z | bibcode = 2024Natur.626..271M | url = https://www.repository.cam.ac.uk/handle/1810/364692 }}</ref><ref name="Bahat-2021" />

Mitochondria contribute to apoptosis by releasing [[Cytochrome c|cytochrome ''c'']], which directly induces the formation of [[apoptosome]]s. Additionally, they are a source of various [[damage-associated molecular pattern]]s (DAMPs). These DAMPs are often recognised by the same [[Pattern recognition receptor|pattern-recognition receptors]] (PRRs) that respond to [[pathogen-associated molecular pattern]]s (PAMPs) during infections.{{refn|{{cite journal | vauthors = Krysko DV, Agostinis P, Krysko O, Garg AD, Bachert C, Lambrecht BN, Vandenabeele P | title = Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation | journal = Trends in Immunology | volume = 32 | issue = 4 | pages = 157–164 | date = April 2011 | pmid = 21334975 | doi = 10.1016/j.it.2011.01.005 | url = https://lirias.kuleuven.be/bitstream/123456789/632510/2/Krysko%20et%20al%20_21-09-10.doc }}; cited in<ref name="Murphy-2024" />}} For example, mitochondrial mtDNA resembles bacterial DNA due to its lack of [[CpG site|CpG]] methylation and can be detected by [[Toll-like receptor 9]] and [[CGAS–STING cytosolic DNA sensing pathway|cGAS]].{{refn|{{cite journal | vauthors = Riley JS, Tait SW | title = Mitochondrial DNA in inflammation and immunity | journal = EMBO Reports | volume = 21 | issue = 4 | pages = e49799 | date = April 2020 | pmid = 32202065 | pmc = 7132203 | doi = 10.15252/embr.201949799 }}; cited in<ref name="Murphy-2024" />}} [[DsRNA|Double-stranded RNA]]  (dsRNA), produced due to bidirectional mitochondrial transcription, can activate viral sensing pathways through [[RIG-I-like receptor]]s.{{refn|{{cite journal | vauthors = Seth RB, Sun L, Ea CK, Chen ZJ | title = Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3 | journal = Cell | volume = 122 | issue = 5 | pages = 669–682 | date = September 2005 | pmid = 16125763 | doi = 10.1016/j.cell.2005.08.012 }}; cited in<ref name="Murphy-2024" />}} Additionally, the ''N''-formylation of [[Human mitochondrial genetics|mitochondrial proteins]], similar to that of bacterial proteins, can be recognized by [[formyl peptide receptor]]s.{{refn|{{cite journal | vauthors = Dorward DA, Lucas CD, Doherty MK, Chapman GB, Scholefield EJ, Conway Morris A, Felton JM, Kipari T, Humphries DC, Robb CT, Simpson AJ, Whitfield PD, Haslett C, Dhaliwal K, Rossi AG | title = Novel role for endogenous mitochondrial formylated peptide-driven formyl peptide receptor 1 signalling in acute respiratory distress syndrome | journal = Thorax | volume = 72 | issue = 10 | pages = 928–936 | date = October 2017 | pmid = 28469031 | pmc = 5738532 | doi = 10.1136/thoraxjnl-2017-210030 }}; cited in<ref name="Murphy-2024" />}}{{refn|{{cite journal | vauthors = Cai N, Gomez-Duran A, Yonova-Doing E, Kundu K, Burgess AI, Golder ZJ, Calabrese C, Bonder MJ, Camacho M, Lawson RA, Li L, Williams-Gray CH, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Stewart ID, Pietzner M, Wareham NJ, Langenberg C, Danesh J, Walter K, Rothwell PM, Howson JM, Stegle O, Chinnery PF, Soranzo N | title = Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases | journal = Nature Medicine | volume = 27 | issue = 9 | pages = 1564–1575 | date = September 2021 | pmid = 34426706 | doi = 10.1038/s41591-021-01441-3 | first14 = Emanuele | first15 = David J. | hdl = 10261/249231 | hdl-access = free }}; cited in<ref name="Murphy-2024" />}}

Normally, these mitochondrial components are sequestered from the rest of the cell but are released following mitochondrial membrane permeabilization during apoptosis or passively after mitochondrial damage. However, mitochondria also play an active role in innate immunity, releasing mtDNA in response to metabolic cues.<ref name="Bahat-2021" /> Mitochondria are also the [[Subcellular localization|localization site]] for immune and apoptosis regulatory proteins, such as [[Apoptosis regulator BAX|BAX]], [[Mitochondrial antiviral-signaling protein|MAVS]] (located on the [[Mitochondrion#Outer membrane|outer membrane]]), and [[NLRX1]] (found in the [[Mitochondrion#Matrix|matrix]]). These proteins are modulated by the mitochondrial metabolic status and mitochondrial dynamics.<ref name="Bahat-2021" />{{refn|{{cite journal | vauthors = Zhang W, Wang G, Xu ZG, Tu H, Hu F, Dai J, Chang Y, Chen Y, Lu Y, Zeng H, Cai Z, Han F, Xu C, Jin G, Sun L, Pan BS, Lai SW, Hsu CC, Xu J, Chen ZZ, Li HY, Seth P, Hu J, Zhang X, Li H, Lin HK | title = Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS | journal = Cell | volume = 178 | issue = 1 | pages = 176–189.e15 | date = June 2019 | pmid = 31155231 | pmc = 6625351 | doi = 10.1016/j.cell.2019.05.003 }}; cited in<ref name="Bahat-2021" />}}{{refn|{{cite journal | vauthors = Pourcelot M, Arnoult D | title = Mitochondrial dynamics and the innate antiviral immune response | journal = The FEBS Journal | volume = 281 | issue = 17 | pages = 3791–3802 | date = September 2014 | pmid = 25051991 | doi = 10.1111/febs.12940 }}; cited in<ref name="Bahat-2021" />}}

=== Donation ===
Some cells donate mitochondria to other cells. Such donations occur in multiple cell types, in organisms such as yeast, molluscs, and rodents. Mitochondrial donation was first observed in 2006. As of 2025, it had not been observed in humans ''[[in vivo]]''. Donations may occur to help damaged cells, trigger tissue repair or the immune system, or to power distressed cells.<ref name=":0">{{Cite journal |last=Conroy |first=Gemma |date=2025-04-08 |title=Cells are swapping their mitochondria. What does this mean for our health? |url=https://www.nature.com/articles/d41586-025-01064-5 |journal=Nature |language=en |volume=640 |issue=8058 |pages=302–304 |doi=10.1038/d41586-025-01064-5 |pmid=40200117 |issn=1476-4687}}</ref>

Researchers cultured human mitochondria-free lung cancer cells with stem cells. The stem cells ejected mitochondria, which were absorbed by the lung cells. The lung cells then recovered their ability to divide and metabolize glucose. Mitochondria were then detected moving among lung, heart, brain, fat, bone, and other cells. Research has not identified how a cell indicates that it needs mitochondrial assistance or how other cells read those indicators.<ref name=":0" />

Various purposes have been observed to explain such donations. These include:<ref name=":0" />

* Restore function and extending lifespans of damaged cells<ref>{{Cite journal |last1=Spees |first1=Jeffrey L. |last2=Olson |first2=Scott D. |last3=Whitney |first3=Mandolin J. |last4=Prockop |first4=Darwin J. |date=2006-01-31 |title=Mitochondrial transfer between cells can rescue aerobic respiration |journal=Proceedings of the National Academy of Sciences |volume=103 |issue=5 |pages=1283–1288 |doi=10.1073/pnas.0510511103 |doi-access=free |pmc=1345715 |pmid=16432190|bibcode=2006PNAS..103.1283S }}</ref><ref>{{Cite journal |last1=Ahmad |first1=Tanveer |last2=Mukherjee |first2=Shravani |last3=Pattnaik |first3=Bijay |last4=Kumar |first4=Manish |last5=Singh |first5=Suchita |last6=Kumar |first6=Manish |last7=Rehman |first7=Rakhshinda |last8=Tiwari |first8=Brijendra K |last9=Jha |first9=Kumar A |last10=Barhanpurkar |first10=Amruta P |last11=Wani |first11=Mohan R |last12=Roy |first12=Soumya S |last13=Mabalirajan |first13=Ulaganathan |last14=Ghosh |first14=Balaram |last15=Agrawal |first15=Anurag |date=January 2014 |title=Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy |url=https://doi.org/10.1002/embj.201386030 |journal=The EMBO Journal |volume=33 |issue=9 |pages=994–1010 |doi=10.1002/embj.201386030 |pmid=24431222 |pmc=4193933 |issn=0261-4189}}</ref><ref>{{Cite journal |last1=Hayakawa |first1=Kazuhide |last2=Esposito |first2=Elga |last3=Wang |first3=Xiaohua |last4=Terasaki |first4=Yasukazu |last5=Liu |first5=Yi |last6=Xing |first6=Changhong |last7=Ji |first7=Xunming |last8=Lo |first8=Eng H. |date=July 2016 |title=Transfer of mitochondria from astrocytes to neurons after stroke |journal=Nature |language=en |volume=535 |issue=7613 |pages=551–555 |doi=10.1038/nature18928 |pmid=27466127 |pmc=4968589 |bibcode=2016Natur.535..551H |issn=1476-4687}}</ref>
* Endothelial cell donation to cancer cells can increase chemoresistance<ref>{{Cite journal |last1=Pasquier |first1=Jennifer |last2=Guerrouahen |first2=Bella S. |last3=Al Thawadi |first3=Hamda |last4=Ghiabi |first4=Pegah |last5=Maleki |first5=Mahtab |last6=Abu-Kaoud |first6=Nadine |last7=Jacob |first7=Arthur |last8=Mirshahi |first8=Massoud |last9=Galas |first9=Ludovic |last10=Rafii |first10=Shahin |last11=Le Foll |first11=Frank |last12=Rafii |first12=Arash |date=2013-04-10 |title=Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance |journal=Journal of Translational Medicine |volume=11 |issue=1 |pages=94 |doi=10.1186/1479-5876-11-94 |doi-access=free |issn=1479-5876 |pmc=3668949 |pmid=23574623}}</ref> or tumorigenic potential.<ref>{{Cite journal |last1=Tan |first1=An S. |last2=Baty |first2=James W. |last3=Dong |first3=Lan-Feng |last4=Bezawork-Geleta |first4=Ayenachew |last5=Endaya |first5=Berwini |last6=Goodwin |first6=Jacob |last7=Bajzikova |first7=Martina |last8=Kovarova |first8=Jaromira |last9=Peterka |first9=Martin |last10=Yan |first10=Bing |last11=Pesdar |first11=Elham Alizadeh |last12=Sobol |first12=Margarita |last13=Filimonenko |first13=Anatolyj |last14=Stuart |first14=Shani |last15=Vondrusova |first15=Magdalena |date=2015-01-06 |title=Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA |url=https://pubmed.ncbi.nlm.nih.gov/25565207 |journal=Cell Metabolism |volume=21 |issue=1 |pages=81–94 |doi=10.1016/j.cmet.2014.12.003 |issn=1932-7420 |pmid=25565207}}</ref>
* Following acute lung injury, stromal cells can donate mitochondria to lung cells, which in turn distributed ATP (fuel) to nearby cells that did not receive mitochondria.<ref>{{Cite journal |last1=Islam |first1=Mohammad Naimul |last2=Das |first2=Shonit R. |last3=Emin |first3=Memet T. |last4=Wei |first4=Michelle |last5=Sun |first5=Li |last6=Westphalen |first6=Kristin |last7=Rowlands |first7=David J. |last8=Quadri |first8=Sadiqa K. |last9=Bhattacharya |first9=Sunita |last10=Bhattacharya |first10=Jahar |date=May 2012 |title=Mitochondrial transfer from bone-marrow–derived stromal cells to pulmonary alveoli protects against acute lung injury |journal=Nature Medicine |language=en |volume=18 |issue=5 |pages=759–765 |doi=10.1038/nm.2736 |pmid=22504485 |pmc=3727429 |issn=1546-170X}}</ref>
* Platelets can donate mitochondria to stem cells which then release molecules that aid in blood vessel formation, which accelerates wound healing. Bone cell donations had a similar effect.
* Maintain the blood-brain barrier
* Maintain macrophage function when their metabolism is disrupted
* Reduce inflammatory response, particularly when donated to T cells. Stem cells cultured from rheumatoid arthritis patients donated fewer mitochondria to T cells than do those from others.

Extracellular mitochondria use multiple modes of transport:<ref name=":0" />

** tunnelling nanotubes that temporarily connect cells to transport various cargo<ref>{{Cite journal |last1=Wang |first1=X. |last2=Gerdes |first2=H.-H. |date=July 2015 |title=Transfer of mitochondria via tunneling nanotubes rescues apoptotic PC12 cells |url=https://www.nature.com/articles/cdd2014211 |journal=Cell Death & Differentiation |language=en |volume=22 |issue=7 |pages=1181–1191 |doi=10.1038/cdd.2014.211 |issn=1476-5403|hdl=1956/10814 |hdl-access=free }}</ref>
** passengers on [[Vesicle (biology and chemistry)|vesicles]] 
** free-floating (typically in blood)
** cell contact/fusion

=== Additional functions ===
Mitochondria play a central role in many other [[metabolism|metabolic]] tasks, such as:
* Signaling through mitochondrial [[reactive oxygen species]]<ref name="Li-2013">{{cite journal | vauthors = Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF | title = Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers | journal = Journal of Hematology & Oncology | volume = 6 | issue = 19 | pages = 19 | date = February 2013 | pmid = 23442817 | pmc = 3599349 | doi = 10.1186/1756-8722-6-19 | doi-access = free }}</ref>
* Regulation of the [[membrane potential]]<ref name="Voet-2006"/>
* Calcium signaling (including calcium-evoked apoptosis)<ref>{{cite journal | vauthors = Hajnóczky G, Csordás G, Das S, Garcia-Perez C, Saotome M, Sinha Roy S, Yi M | title = Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis | journal = Cell Calcium | volume = 40 | issue = 5–6 | pages = 553–560 | year = 2006 | pmid = 17074387 | pmc = 2692319 | doi = 10.1016/j.ceca.2006.08.016 }}</ref>
* Regulation of cellular [[metabolism]]<ref name="McBride-2006">{{cite journal | vauthors = McBride HM, Neuspiel M, Wasiak S | title = Mitochondria: more than just a powerhouse | journal = Current Biology | volume = 16 | issue = 14 | pages = R551–R560 | date = July 2006 | pmid = 16860735 | doi = 10.1016/j.cub.2006.06.054 | doi-access = free | bibcode = 2006CBio...16.R551M }}</ref>
* Certain [[heme]] synthesis reactions<ref>{{cite journal | vauthors = Oh-hama T | title = Evolutionary consideration on 5-aminolevulinate synthase in nature | journal = Origins of Life and Evolution of the Biosphere | volume = 27 | issue = 4 | pages = 405–412 | date = August 1997 | pmid = 9249985 | doi = 10.1023/A:1006583601341 | bibcode = 1997OLEB...27..405O }}</ref> (see also: ''[[Porphyrin]]'')
* [[Steroid]] synthesis<ref name="Rossier-2006">{{cite journal | vauthors = Rossier MF | title = T channels and steroid biosynthesis: in search of a link with mitochondria | journal = Cell Calcium | volume = 40 | issue = 2 | pages = 155–164 | date = August 2006 | pmid = 16759697 | doi = 10.1016/j.ceca.2006.04.020 }}</ref>
* Hormonal signaling<ref>{{cite journal | vauthors = Klinge CM | title = Estrogenic control of mitochondrial function and biogenesis | journal = Journal of Cellular Biochemistry | volume = 105 | issue = 6 | pages = 1342–1351 | date = December 2008 | pmid = 18846505 | pmc = 2593138 | doi = 10.1002/jcb.21936 }}</ref> – mitochondria are sensitive and responsive to hormones, in part by the action of mitochondrial estrogen receptors (mtERs). These receptors have been found in various tissues and cell types, including brain<ref>{{cite journal | vauthors = Alvarez-Delgado C, Mendoza-Rodríguez CA, Picazo O, Cerbón M | title = Different expression of alpha and beta mitochondrial estrogen receptors in the aging rat brain: interaction with respiratory complex V | journal = Experimental Gerontology | volume = 45 | issue = 7–8 | pages = 580–585 | date = August 2010 | pmid = 20096765 | doi = 10.1016/j.exger.2010.01.015 }}</ref> and heart<ref>{{cite journal | vauthors = Pavón N, Martínez-Abundis E, Hernández L, Gallardo-Pérez JC, Alvarez-Delgado C, Cerbón M, Pérez-Torres I, Aranda A, Chávez E | title = Sexual hormones: effects on cardiac and mitochondrial activity after ischemia-reperfusion in adult rats. Gender difference | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 132 | issue = 1–2 | pages = 135–146 | date = October 2012 | pmid = 22609314 | doi = 10.1016/j.jsbmb.2012.05.003 }}</ref>
* Development and function of immune cells<ref>{{cite journal | vauthors = Breda CN, Davanzo GG, Basso PJ, Saraiva Câmara NO, Moraes-Vieira PM | title = Mitochondria as central hub of the immune system | journal = Redox Biology | volume = 26 | pages = 101255 | date = September 2019 | pmid = 31247505 | pmc = 6598836 | doi = 10.1016/j.redox.2019.101255 }}</ref>
* Neuronal mitochondria also contribute to cellular quality control by reporting neuronal status towards microglia through specialised somatic-junctions.<ref name="Cserép-2020"/>
* Mitochondria of developing neurons contribute to intercellular signaling towards [[microglia]], which communication is indispensable for proper regulation of brain development.<ref>{{cite journal | vauthors = Cserép C, Schwarcz AD, Pósfai B, László ZI, Kellermayer A, Környei Z, Kisfali M, Nyerges M, Lele Z, Katona I | title = Microglial control of neuronal development via somatic purinergic junctions | journal = Cell Reports | volume = 40 | issue = 12 | pages = 111369 | date = September 2022 | pmid = 36130488 | pmc = 9513806 | doi = 10.1016/j.celrep.2022.111369 }}</ref>

Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in [[liver cell]]s 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 disease]]s.

Mitochondrial proteins (proteins transcribed from mitochondrial DNA) vary depending on the tissue and the species. In humans, 615 distinct types of proteins have been identified from [[heart|cardiac]] mitochondria,<ref>{{cite journal | vauthors = Taylor SW, Fahy E, Zhang B, Glenn GM, Warnock DE, Wiley S, Murphy AN, Gaucher SP, Capaldi RA, Gibson BW, Ghosh SS | title = Characterization of the human heart mitochondrial proteome | journal = Nature Biotechnology | volume = 21 | issue = 3 | pages = 281–286 | date = March 2003 | pmid = 12592411 | doi = 10.1038/nbt793 }}</ref> whereas in [[Murinae|rats]], 940 proteins have been reported.<ref>{{cite journal | vauthors = Zhang J, Li X, Mueller M, Wang Y, Zong C, Deng N, Vondriska TM, Liem DA, Yang JI, Korge P, Honda H, Weiss JN, Apweiler R, Ping P | title = Systematic characterization of the murine mitochondrial proteome using functionally validated cardiac mitochondria | journal = Proteomics | volume = 8 | issue = 8 | pages = 1564–1575 | date = April 2008 | pmid = 18348319 | pmc = 2799225 | doi = 10.1002/pmic.200700851 }}</ref> The mitochondrial [[proteome]] is thought to be dynamically regulated.<ref>{{cite journal | vauthors = Zhang J, Liem DA, Mueller M, Wang Y, Zong C, Deng N, Vondriska TM, Korge P, Drews O, Maclellan WR, Honda H, Weiss JN, Apweiler R, Ping P | title = Altered proteome biology of cardiac mitochondria under stress conditions | journal = Journal of Proteome Research | volume = 7 | issue = 6 | pages = 2204–2214 | date = June 2008 | pmid = 18484766 | pmc = 3805274 | doi = 10.1021/pr070371f }}</ref>