Mitochondrial permeability transition pore

Andrabi, S. A., Sayeed, I., Siemen, D., Wolf, G. Horn, T. F. (2004). Direct inhibition of the mitochondrial permeability transition pore a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J. 18, 869-71. 

A dissipation of mitochondrial membrane potential (A P/w) is often detectable dining apoptosis (Green, 1998 Shidoji et al, 1997). A loss of A Pm is thonght to be mediated by the opening of the mitochondrial permeability transition pore which is proposed to be involved in mitochondrial efflux of cytochrome c into the cytosol (Scarlett and Mnrphy, 1997). However, a recent report by Bossy-Wetzel et al (1998) provided... 

Scorrano, L., PetroniUi, V., Di Lisa, F., and Bemardi, P., 1999, Commitment to apoptosis by GD3 ganglioside depends on opening ofthe mitochondrial permeability transition pore. J Biol Chem 274 22581-22585. 

Kroemer G. The mitochondrial permeability transition pore complex as a pharmacological target. An introduction. Curr Med Chem 2003 10(16) 1469-1472. 

Kidd JF, Pilkington MF, Schell MJ, et al. Paclitaxel affects cytosolic calcium signals by opening the mitochondrial permeability transition pore. J Biol Chem 2002 277(8) 6504-6510. 

Much progress has been made in understanding the different mechanisms that can cause mitochondrial dysfunction, such as (i) uncoupling of electron transport from ATP synthesis by undermining integrity of inner membrane (ii) direct inhibition of electron transport system components (iii) opening of the mitochondrial permeability transition pore leading to irreversible collapse of the transmembrane potential and release of pro-apoptotic factors (iv) inhibition of the... 

Drugs that Induce the Mitochondrial Permeability Transition Pore (MPT)... 

Juhaszova, M. et al. (2008) The identity and regulation of the mitochondrial permeability transition pore where the known meets the unknown. Annals of the New York Academy of Sciences, 1123, 197-212. 

The structure of doxorubicin includes a quinone moiety therefore, it can easily accept an electron and undergo redox cycling (Fig. 7.47). Because it accumulates in the mitochondria, it can accept electrons from the electron transport chain and divert them away from complex I. It becomes reduced to the semiquinone radical in the process. This will then reduce oxygen to superoxide and return to the quinone form (Fig. 7.47). This could lead to oxidation of GSH and mtDNA. The subsequent damage may lead to the opening of the mitochondrial permeability transition pore. Consequently, mitochondrial ATP production will be compromised, and ATP levels will decline. 

Halestrap AP, Clarke SJ, Javadov SA (2004) Mitochondrial permeability transition pore opening during myocardial reperfusion - a target for cardioprotection. Cardiovasc Res 61(3) 372—385 Harrison GJ, Cemiway RJ, Peart J, Berr SS, Ashton K, Regan S, Matheme GP, Headrick JP (2002) Effects of A3 adenosine receptor activation and gene knock-out in ischemic-reperfused mouse heart. Cardiovasc Res 53(1) 147-155... 

Hausenloy D, Wynne A, Duchen M, Yellon D (2004) Transient mitochondrial permeability transition pore opening mediates preconditioning-induced protection. Circulation 109(14) 1714—1717... 

Bernardi, P., Vassanelli, S., Veronese, P., Colonna, R., Szabo, I., and Zoratti, M., 1992, Modulation of the mitochondrial permeability transition pore. Effect of protons and divalent cations, J. Biol. Chem. 

Crompton, M., 1999, The mitochondrial permeability transition pore and its role in cell death, Biochem. 

Feldmann, G., Haouzi, D., Moreau, A., Durand, S. A., Bringuier, A., Berson, A., Mansouri, A., Fau, D., and Pessayre, D., 2000, Opening of the mitochondrial permeability transition pore causes matrix expansion and outer membrane rupture in Fas-mediated hepatic apoptosis in mice, Hepatology 31, pp. 674-683... 

Juhaszova, M., Zorov, D.B., Kim, S.H., Pepe, S., Fu, Q., Fishbein, K.W., Ziman, B.D., Wang, S., Ytrehus, K., Antos, C.L., Olson, E.N., and Sollott, SJ. 2004. Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin. Invest. 113 1535-1549. 

Halestrap, A.P., Clarke, S.J., and Javadov, S.A. 2004. Mitochondrial permeability transition pore opening during myocardial reperfusion—a target for cardioprotection. Cardiovasc. Res. 61 372-385. 

Ricci, C., Pastukh, V., and Schaffer, S. 2005. Involvement of the mitochondrial permeability transition pore in angiotensin II-mediated apoptosis. Exp. Clin. Cardiol. 10 160-164. 

Crompton M, Virji S, Doyle V, Johnson N, Ward JM (1999), The mitochondrial permeability transition pore, Biochem. Soc. Symp. 66 167-179. 

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