On Air

Investment

Buy this Domain?
Do you interesting about this domain and the running project?
Feel free to send your offer to webmaster.
pay with Paypal

Advertising

Mitochondrial permeability transition pore

The mitochondrial permeability transition pore (mPTP or MPTP; also referred to as PTP, mTP or MTP) is a protein that is formed in the inner membrane of the mitochondria under certain pathological conditions such as traumatic brain injury and stroke. Opening allows increase in the permeability of the mitochondrial membranes to molecules of less than 1500 Daltons in molecular weight. Induction of the permeability transition pore, mitochondrial membrane permeability transition (mPT or MPT), can lead to mitochondrial swelling and cell death through apoptosis or necrosis depending on the particular biological setting.{{Cite journal | last1 = Lemasters | first1 = J. J. | last2 = Theruvath | first2 = T. P. | last3 = Zhong | first3 = Z. | last4 = Nieminen | first4 = A. L. | title = Mitochondrial calcium and the permeability transition in cell death | doi = 10.1016/j.bbabio.2009.06.009 | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1787 | issue = 11 | pages = 1395–1401 | year = 2009 | pmid = 19576166 | pmc =2730424 }}

Roles in pathology

The MPTP was originally discovered by Haworth and Hunter{{Cite journal | last1 = Haworth | first1 = R. A. | last2 = Hunter | first2 = D. R. | title = The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site | journal = Archives of Biochemistry and Biophysics | volume = 195 | issue = 2 | pages = 460–467 | year = 1979 | pmid = 38751 | doi=10.1016/0003-9861(79)90372-2 }} in 1979 and has been found to be involved in neurodegeneration, hepatotoxicity from Reye-related agents, cardiac necrosis and nervous and muscular dystrophies among other deleterious events inducing cell damage and death.{{Cite journal | last1 = Fiskum | first1 = G. | title = Mitochondrial participation in ischemic and traumatic neural cell death | journal = Journal of Neurotrauma | volume = 17 | issue = 10 | pages = 843–855 | year = 2000 | pmid = 11063052 | doi=10.1089/neu.2000.17.843 }}{{Cite journal | last1 = Bernardi | first1 = P. | last2 = Bonaldo | first2 = P. | doi = 10.1196/annals.1427.009 | title = Dysfunction of Mitochondria and Sarcoplasmic Reticulum in the Pathogenesis of Collagen VI Muscular Dystrophies | journal = Annals of the New York Academy of Sciences | volume = 1147 | pages = 303–311 | year = 2008 | pmid = 19076452 | pmc = }}{{Cite journal | last1 = Baines | first1 = C. P. | doi = 10.1146/annurev-physiol-021909-135929 | title = The Cardiac Mitochondrion: Nexus of Stress | journal = Annual Review of Physiology | volume = 72 | pages = 61–80 | year = 2010 | pmid = 20148667 | pmc = }} MPT is one of the major causes of cell death in a variety of conditions. For example, it is key in neuronal cell death in excitotoxicity, in which overactivation of glutamate receptors causes excessive calcium entry into the cell.{{Cite journal | doi = 10.1016/S0005-2728(98)00119-4 | last1 = Ichas | first1 = F. | last2 = Mazat | first2 = J. P. | title = From calcium signaling to cell death: Two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state | journal = Biochimica et Biophysica Acta | volume = 1366 | issue = 1–2 | pages = 33–50 | year = 1998 | pmid = 9714722 }}{{Cite journal | last1 = Schinder | first1 = A. F. | last2 = Olson | first2 = E. C. | last3 = Spitzer | first3 = N. C. | last4 = Montal | first4 = M. | title = Mitochondrial dysfunction is a primary event in glutamate neurotoxicity | journal = The Journal of Neuroscience | volume = 16 | issue = 19 | pages = 6125–6133 | year = 1996 | pmid = 8815895 }}{{Cite journal | last1 = White | first1 = R. J. | last2 = Reynolds | first2 = I. J. | title = Mitochondrial depolarization in glutamate-stimulated neurons: An early signal specific to excitotoxin exposure | journal = The Journal of Neuroscience | volume = 16 | issue = 18 | pages = 5688–5697 | year = 1996 | pmid = 8795624 }} MPT also appears to play a key role in damage caused by ischemia, as occurs in a heart attack and stroke.{{Cite journal | last1 = Honda | first1 = H. M. | last2 = Ping | first2 = P. | doi = 10.1007/s10557-006-0642-0 | title = Mitochondrial Permeability Transition in Cardiac Cell Injury and Death | journal = Cardiovascular Drugs and Therapy | volume = 20 | issue = 6 | pages = 425–432 | year = 2006 | pmid = 17171295 | pmc = }} However, research has shown that the MPT pore remains closed during ischemia, but opens once the tissues are reperfused with blood after the ischemic period,{{Cite journal | last1 = Bopassa | first1 = J. C. | last2 = Michel | first2 = P. | last3 = Gateau-Roesch | first3 = O. | last4 = Ovize | first4 = M. | last5 = Ferrera | first5 = R. | title = Low-pressure reperfusion alters mitochondrial permeability transition | doi = 10.1152/ajpheart.01081.2004 | journal = AJP: Heart and Circulatory Physiology | volume = 288 | issue = 6 | pages = H2750–H2755 | year = 2005 | pmid = 15653760 | pmc = }} playing a role in reperfusion injury. MPT is also thought to underlie the cell death induced by Reye's syndrome, since chemicals that can cause the syndrome, like salicylate and valproate, cause MPT.{{Cite journal | doi = 10.1016/S0005-2728(98)00112-1 | last1 = Lemasters | first1 = J. J. | last2 = Nieminen | first2 = A. L. | last3 = Qian | first3 = T. | last4 = Trost | first4 = L. C. | last5 = Elmore | first5 = S. P. | last6 = Nishimura | first6 = Y. | last7 = Crowe | first7 = R. A. | last8 = Cascio | first8 = W. E. | last9 = Bradham | first9 = C. A. | last10 = Brenner | first10 = D. A. | last11 = Herman | first11 = B. | title = The mitochondrial permeability transition in cell death: A common mechanism in necrosis, apoptosis and autophagy | journal = Biochimica et Biophysica Acta | volume = 1366 | issue = 1–2 | pages = 177–196 | year = 1998 | pmid = 9714796 }} MPT may also play a role in mitochondrial autophagy. Cells exposed to toxic amounts of Ca2+ ionophores also undergo MPT and death by necrosis.

MPTP Structure

While the MPT modulation has been widely studied, little is known about its structure{{Cite journal |last1 = Srinivasan | first1 = B. | title = Mitochondrial permeability transition pore: an enigmatic gatekeeper | journal = New Horizons in Science & Technology (NHS&T) | volume = 1 | issue = 3 | pages = 47–51 | year = 2012 | ISSN = 1929-2015 | url = https://www.researchgate.net/publication/272153136_Mitochondrial_permeability_transition_pore_an_enigmatic_gatekeeper}} . Initial experiments by Szabó and Zoratti proposed the MPT may comprise Voltage Dependent Anion Channel (VDAC) molecules. Nevertheless, this hypothesis was shown to be incorrect as VDAC−/− mitochondria were still capable to undergo MPT.{{Cite journal | last1 = Szabó | first1 = I. | last2 = Zoratti | first2 = M. | title = The mitochondrial permeability transition pore may comprise VDAC molecules. I. Binary structure and voltage dependence of the pore | journal = FEBS Letters | volume = 330 | issue = 2 | pages = 201–205 | year = 1993 | pmid = 7689983 | doi=10.1016/0014-5793(93)80273-w }}{{Cite journal | last1 = Baines | first1 = C. P. | last2 = Kaiser | first2 = R. A. | last3 = Sheiko | first3 = T. | last4 = Craigen | first4 = W. J. | last5 = Molkentin | first5 = J. D. | title = Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death | doi = 10.1038/ncb1575 | journal = Nature Cell Biology | volume = 9 | issue = 5 | pages = 550–555 | year = 2007 | pmid = 17417626 | pmc =2680246 }} Further hypothesis by Halestrap´s group convincingly suggested the MPT was formed by the inner membrane Adenine Nucleotide Translocase (ANT), but genetic ablation of such protein still led to MPT onset.{{Cite journal | last1 = Kokoszka | first1 = J. E. | last2 = Waymire | first2 = K. G. | last3 = Levy | first3 = S. E. | last4 = Sligh | first4 = J. E. | last5 = Cai | first5 = J. | last6 = Jones | first6 = D. P. | last7 = MacGregor | first7 = G. R. | last8 = Wallace | first8 = D. C. | doi = 10.1038/nature02229 | title = The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore | journal = Nature | volume = 427 | issue = 6973 | pages = 461–465 | year = 2004 | pmid = 14749836 | pmc =3049806 }}{{Cite journal | last1 = Varanyuwatana | first1 = P. | last2 = Halestrap | first2 = A. P. | doi = 10.1016/j.mito.2011.04.006 | title = The roles of phosphate and the phosphate carrier in the mitochondrial permeability transition pore | journal = Mitochondrion | volume = 12 | issue = 1 | pages = 120–125 | year = 2012 | pmid = 21586347 | pmc =3281194 }} Thus, the only MPTP components identified so far are the TSPO (previously known as the peripheral benzodiazepine receptor) located in the mitochondrial outer membrane and cyclophilin-D in the mitochondrial matrix.{{Cite journal | last1 = Sileikyte | first1 = J. | last2 = Petronilli | first2 = V. | last3 = Zulian | first3 = A. | last4 = Dabbeni-Sala | first4 = F. | last5 = Tognon | first5 = G. | last6 = Nikolov | first6 = P. | last7 = Bernardi | first7 = P. | last8 = Ricchelli | first8 = F. | doi = 10.1074/jbc.M110.172486 | title = Regulation of the Inner Membrane Mitochondrial Permeability Transition by the Outer Membrane Translocator Protein (Peripheral Benzodiazepine Receptor) | journal = Journal of Biological Chemistry | volume = 286 | issue = 2 | pages = 1046–1053 | year = 2010 | pmid = 21062740 | pmc =3020711 }}{{Cite journal | last1 = Baines | first1 = C. P. | last2 = Kaiser | first2 = R. A. | last3 = Purcell | first3 = N. H. | last4 = Blair | first4 = N. S. | last5 = Osinska | first5 = H. | last6 = Hambleton | first6 = M. A. | last7 = Brunskill | first7 = E. W. | last8 = Sayen | first8 = M. R. | last9 = Gottlieb | first9 = R. A. | last10 = Dorn | doi = 10.1038/nature03434 | first10 = G. W. | last11 = Robbins | first11 = J. | last12 = Molkentin | first12 = J. D. | title = Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death | journal = Nature | volume = 434 | issue = 7033 | pages = 658–662 | year = 2005 | pmid = 15800627 | pmc = }} Mice lacking the gene for cyclophilin-D develop normally, but their cells do not undergo Cyclosporin A-sensitive MPT, and they are resistant to necrotic death from ischemia or overload of Ca2+ or free radicals.{{Cite journal | last1 = Nakagawa | first1 = T. | last2 = Shimizu | first2 = S. | last3 = Watanabe | first3 = T. | last4 = Yamaguchi | first4 = O. | last5 = Otsu | first5 = K. | last6 = Yamagata | first6 = H. | last7 = Inohara | first7 = H. | last8 = Kubo | first8 = T. | last9 = Tsujimoto | first9 = Y. | doi = 10.1038/nature03317 | title = Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death | journal = Nature | volume = 434 | issue = 7033 | pages = 652–658 | year = 2005 | pmid = 15800626 | pmc = }} However, these cells do die in response to stimuli that kill cells through apoptosis, suggesting that MPT does not control cell death by apoptosis.

MPTP blockers

Agents that transiently block MPT include the immune suppressant cyclosporin A (CsA); N-methyl-Val-4-cyclosporin A (MeValCsA), a non- immunosuppressant derivative of CsA; another non-immunosuppressive agent, NIM811, 2-aminoethoxydiphenyl borate (2-APB),{{Cite journal | last1 = Chinopoulos | first1 = C. | last2 = Starkov | first2 = A. A. | last3 = Fiskum | first3 = G. | doi = 10.1074/jbc.M303808200 | title = Cyclosporin A-insensitive Permeability Transition in Brain Mitochondria: INHIBITION BY 2-AMINOETHOXYDIPHENYL BORATE | journal = Journal of Biological Chemistry | volume = 278 | issue = 30 | pages = 27382–27389 | year = 2003 | pmid = 12750371 | pmc = }} bongkrekic acid and alisporivir (also known as Debio-025). TRO40303 is a newly synthetitised MPT blocker developed by Trophos company and currently is in Phase I clinical trial.

Factors in MPT induction

Various factors enhance the likelihood of MPTP opening. In some mitochondria, such as those in the central nervous system, high levels of Ca2+ within mitochondria can cause the MPT pore to open.{{Cite journal | last1 = Brustovetsky | first1 = N. | last2 = Brustovetsky | first2 = T. | last3 = Jemmerson | first3 = R. | last4 = Dubinsky | first4 = J. M. | title = Calcium-induced cytochrome c release from CNS mitochondria is associated with the permeability transition and rupture of the outer membrane | journal = Journal of Neurochemistry | volume = 80 | issue = 2 | pages = 207–218 | year = 2002 | pmid = 11902111 | doi=10.1046/j.0022-3042.2001.00671.x }}{{Cite journal | doi = 10.1016/0003-9861(79)90371-0 | last1 = Hunter | first1 = D. R. | last2 = Haworth | first2 = R. A. | title = The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms | journal = Archives of Biochemistry and Biophysics | volume = 195 | issue = 2 | pages = 453–459 | year = 1979 | pmid = 383019 }} This is possibly because Ca2+ binds to and activates Ca2+ binding sites on the matrix side of the MPTP. MPT induction is also due to the dissipation of the difference in voltage across the inner mitochondrial membrane (known as transmembrane potential, or Δψ). In neurons and astrocytes, the contribution of membrane potential to MPT induction is complex, see. The presence of free radicals, another result of excessive intracellular calcium concentrations, can also cause the MPT pore to open.{{Cite journal | last1 = Brustovetsky | first1 = N. | last2 = Brustovetsky | first2 = T. | last3 = Purl | first3 = K. J. | last4 = Capano | first4 = M. | last5 = Crompton | first5 = M. | last6 = Dubinsky | first6 = J. M. | title = Increased susceptibility of striatal mitochondria to calcium-induced permeability transition | journal = The Journal of Neuroscience | volume = 23 | issue = 12 | pages = 4858–4867 | year = 2003 | pmid = 12832508 }} Other factors that increase the likelihood that the MPTP will be induced include the presence of certain fatty acids,{{Cite journal | last1 = García-Ruiz | first1 = C. | last2 = Colell | first2 = A. | last3 = París | first3 = R. | last4 = Fernández-Checa | first4 = J. C. | title = Direct interaction of GD3 ganglioside with mitochondria generates reactive oxygen species followed by mitochondrial permeability transition, cytochrome c release, and caspase activation | journal = FASEB Journal | volume = 14 | issue = 7 | pages = 847–858 | year = 2000 | pmid = 10783138 }} and inorganic phosphate.{{Cite journal | last1 = Nicholls | first1 = D. G. | last2 = Brand | first2 = M. D. | title = The nature of the calcium ion efflux induced in rat liver mitochondria by the oxidation of endogenous nicotinamide nucleotides | journal = The Biochemical Journal | volume = 188 | issue = 1 | pages = 113–118 | year = 1980 | pmid = 7406874 | pmc = 1162544 | doi=10.1042/bj1880113 }} However, these factors cannot open the pore without Ca2+, though at high enough concentrations, Ca2+ alone can induce MPT.{{Cite journal | last1 = Gunter | first1 = T. E. | last2 = Gunter | first2 = K. K. | last3 = Sheu | first3 = S. S. | last4 = Gavin | first4 = C. E. | title = Mitochondrial calcium transport: Physiological and pathological relevance | journal = The American Journal of Physiology | volume = 267 | issue = 2 Pt 1 | pages = C313–C339 | year = 1994 | pmid = 8074170 }} Stress in the endoplasmic reticulum can be a factor in triggering MPT.{{Cite journal | last1 = Deniaud | first1 = A. | last2 = Sharaf El Dein | first2 = O. | last3 = Maillier | first3 = E. | last4 = Poncet | first4 = D. | last5 = Kroemer | first5 = G. | last6 = Lemaire | first6 = C. | last7 = Brenner | first7 = C. | doi = 10.1038/sj.onc.1210638 | title = Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis | journal = Oncogene | volume = 27 | issue = 3 | pages = 285–299 | year = 2007 | pmid = 17700538 | pmc = }} Conditions that cause the pore to close or remain closed include acidic conditions,{{Cite journal | last1 = Friberg | first1 = H. | last2 = Wieloch | first2 = T. | title = Mitochondrial permeability transition in acute neurodegeneration | journal = Biochimie | volume = 84 | issue = 2–3 | pages = 241–250 | year = 2002 | pmid = 12022955 | doi=10.1016/s0300-9084(02)01381-0 }} high concentrations of ADP, high concentrations of ATP,{{Cite journal | last1 = Beutner | first1 = G. | last2 = Rück | first2 = A. | last3 = Riede | first3 = B. | last4 = Brdiczka | first4 = D. | title = Complexes between porin, hexokinase, mitochondrial creatine kinase and adenylate translocator display properties of the permeability transition pore. Implication for regulation of permeability transition by the kinases | journal = Biochimica et Biophysica Acta | volume = 1368 | issue = 1 | pages = 7–18 | year = 1998 | pmid = 9459579 | doi=10.1016/s0005-2736(97)00175-2 }} and high concentrations of NADH. Divalent cations like Mg2+ also inhibit MPT, because they can compete with Ca2+ for the Ca2+ binding sites on the matrix and/or cytoplasmic side of the MPTP.

Effects of MPT

Multiple studies have found the MPT to be a key factor in the damage to neurons caused by excitotoxicity. The induction of MPT, which increases mitochondrial membrane permeability, causes mitochondria to become further depolarized, meaning that Δψ is abolished. When Δψ is lost, protons and some molecules are able to flow across the outer mitochondrial membrane uninhibited. Loss of Δψ interferes with the production of adenosine triphosphate (ATP), the cell's main source of energy, because mitochondria must have an electrochemical gradient to provide the driving force for ATP production. In cell damage resulting from conditions such as neurodegenerative diseases and head injury, opening of the mitochondrial permeability transition pore can greatly reduce ATP production, and can cause ATP synthase to begin hydrolysing, rather than producing, ATP.{{Cite journal | last1 = Stavrovskaya | first1 = I. G. | last2 = Kristal | first2 = B. S. | doi = 10.1016/j.freeradbiomed.2004.11.032 | title = The powerhouse takes control of the cell: Is the mitochondrial permeability transition a viable therapeutic target against neuronal dysfunction and death? | journal = Free Radical Biology and Medicine | volume = 38 | issue = 6 | pages = 687–697 | year = 2005 | pmid = 15721979 | pmc = }} This produces an energy deficit in the cell, just when it most needs ATP to fuel activity of ion pumps such as the Na+/Ca2+ exchanger, which must be activated more than under normal conditions in order to rid the cell of excess calcium. MPT also allows Ca2+ to leave the mitochondrion, which can place further stress on nearby mitochondria, and which can activate harmful calcium-dependent proteases such as calpain. Reactive oxygen species (ROS) are also produced as a result of opening the MPT pore. MPT can allow antioxidant molecules such as glutathione to exit mitochondria, reducing the organelles' ability to neutralize ROS. In addition, the electron transport chain (ETC) may produce more free radicals due to loss of components of the ETC, such as cytochrome c, through the MPTP.{{Cite journal | last1 = Luetjens | first1 = C. M. | last2 = Bui | first2 = N. T. | last3 = Sengpiel | first3 = B. | last4 = Münstermann | first4 = G. | last5 = Poppe | first5 = M. | last6 = Krohn | first6 = A. J. | last7 = Bauerbach | first7 = E. | last8 = Krieglstein | first8 = J. | last9 = Prehn | first9 = J. H. | title = Delayed mitochondrial dysfunction in excitotoxic neuron death: Cytochrome c release and a secondary increase in superoxide production | journal = The Journal of Neuroscience | volume = 20 | issue = 15 | pages = 5715–5723 | year = 2000 | pmid = 10908611 }} Loss of ETC components can lead to escape of electrons from the chain, which can then reduce molecules and form free radicals. MPT causes mitochondria to become permeable to molecules smaller than 1.5 kDa, which, once inside, draw water in by increasing the organelle's osmolar load.{{Cite journal | last1 = Büki | first1 = A. | last2 = Okonkwo | first2 = D. O. | last3 = Wang | first3 = K. K. | last4 = Povlishock | first4 = J. T. | title = Cytochrome c release and caspase activation in traumatic axonal injury | journal = The Journal of Neuroscience | volume = 20 | issue = 8 | pages = 2825–2834 | year = 2000 | pmid = 10751434 }} This event may lead mitochondria to swell and may cause the outer membrane to rupture, releasing cytochrome c. Cytochrome c can in turn cause the cell to go through apoptosis ("commit suicide") by activating pro-apoptotic factors. Other researchers contend that it is not mitochondrial membrane rupture that leads to cytochrome c release, but rather another mechanism, such as translocation of the molecule through channels in the outer membrane, which does not involve the MPTP.{{Cite journal | last1 = Priault | first1 = M. | last2 = Chaudhuri | first2 = B. | last3 = Clow | first3 = A. | last4 = Camougrand | first4 = N. | last5 = Manon | first5 = S. | title = Investigation of bax-induced release of cytochrome c from yeast mitochondria permeability of mitochondrial membranes, role of VDAC and ATP requirement | journal = European Journal of Biochemistry / FEBS | volume = 260 | issue = 3 | pages = 684–691 | year = 1999 | pmid = 10102996 | doi=10.1046/j.1432-1327.1999.00198.x }} Much research has found that the fate of the cell after an insult depends on the extent of MPT. If MPT occurs to only a slight extent, the cell may recover, whereas if it occurs more it may undergo apoptosis. If it occurs to an even larger degree the cell is likely to undergo necrotic cell death.

Possible evolutionary purpose of the MPTP

Although the MPTP has been studied mainly in mitochondria from mammalian sources, mitochondria from diverse species also undergo a similar transition. While its occurrence can be easily detected, its purpose still remains elusive. Some have speculated that the regulated opening of the MPT pore may minimize cell injury by causing ROS-producing mitochondria to undergo selective lysosome-dependent mitophagy during nutrient starvation conditions. Under severe stress/pathologic conditions, MPTP opening would trigger injured cell death mainly through necrosis.Haworth RA and Hunter DR. 2001. Ca2+-induced transition in mitochondria: A cellular catastrophe? Chapter 6 In Mitochondria in pathogenesis. Lemasters JJ and Nieminen AL, eds. Kluwer Academic/Plenum Publishers. New York. Pages 115 - 124. There is controversy about the question of whether the MPTP is able to exist in a harmless, "low-conductance" state. This low-conductance state would not induce MPT and would allow certain molecules and ions to cross the mitochondrial membranes. The low-conductance state may allow small ions like Ca2+ to leave mitochondria quickly, in order to aid in the cycling of Ca2+ in healthy cells.{{Cite journal | last1 = Hunter | first1 = D. R. | last2 = Haworth | first2 = R. A. | title = The Ca2+-induced membrane transition in mitochondria. III. Transitional Ca2+ release | journal = Archives of Biochemistry and Biophysics | volume = 195 | issue = 2 | pages = 468–477 | year = 1979 | pmid = 112926 | doi=10.1016/0003-9861(79)90373-4 }}{{Cite journal | last1 = Altschuld | first1 = R. A. | last2 = Hohl | first2 = C. M. | last3 = Castillo | first3 = L. C. | last4 = Garleb | first4 = A. A. | last5 = Starling | first5 = R. C. | last6 = Brierley | first6 = G. P. | title = Cyclosporin inhibits mitochondrial calcium efflux in isolated adult rat ventricular cardiomyocytes | journal = The American Journal of Physiology | volume = 262 | issue = 6 Pt 2 | pages = H1699–H1704 | year = 1992 | pmid = 1377876 }} If this is the case, MPT may be a harmful side effect of abnormal activity of a usually beneficial MPTP. MPTP has been detected in mitochondria from plants, yeasts, such as Saccharomyces cerevisiae, birds, such as guinea fowl and primitive vertebrates such as the Baltic lamprey.{{Cite journal | last1 = Savina | first1 = M. V. | last2 = Emelyanova | first2 = L. V. | last3 = Belyaeva | first3 = E. A. | doi = 10.1016/j.cbpb.2006.07.011 | title = Bioenergetic parameters of lamprey and frog liver mitochondria during metabolic depression and activity | journal = Comparative Biochemistry and Physiology B | volume = 145 | issue = 3–4 | pages = 296–305 | year = 2006 | pmid = 17070716 | pmc = }} While the permeability transition is evident in mitochondria from these sources, its sensitivity to its classic modulators may differ when compared with mammalian mitochondria. Nevertheless, CsA-insensitive MPTP can be triggered in mammalian mitochondria given appropriate experimental conditions strongly suggesting this event may be a conserved characteristic throughout the eukaryotic domain.{{Cite journal | last1 = Uribe-Carvajal | first1 = S. | last2 = Luévano-Martínez | first2 = L. S. A. | last3 = Guerrero-Castillo | first3 = S. | last4 = Cabrera-Orefice | first4 = A. | last5 = Corona-De-La-Peña | first5 = N. A. | last6 = Gutiérrez-Aguilar | first6 = M. | doi = 10.1016/j.mito.2011.02.004 | title = Mitochondrial Unselective Channels throughout the eukaryotic domain | journal = Mitochondrion | volume = 11 | issue = 3 | pages = 382–390 | year = 2011 | pmid = 21385626 | pmc = }}

See also

References

External links

"green air" © 2007 - Ingo Malchow, Webdesign Neustrelitz
This article based upon the http://en.wikipedia.org/wiki/Mitochondrial_permeability_transition_pore, the free encyclopaedia Wikipedia and is licensed under the GNU Free Documentation License.
Further informations available on the list of authors and history: http://en.wikipedia.org/w/index.php?title=Mitochondrial_permeability_transition_pore&action=history
presented by: Ingo Malchow, Mirower Bogen 22, 17235 Neustrelitz, Germany