The Role of Mitochondria in Necrosis Following Myocardial Ischemia-Reperfusion
Using the recently adopted nomenclature of cell death (Levin et al. 1999), necrosis refers to cell death and disintegration, regardless of the pathway; the modifiers apoptotic and oncotic are used to refer to the mechanism of death. Traditionally cell death following ischemia has been thought to be primarily oncotic necrosis. As detailed in numerous reviews, during ischemia when the ATP falls to very low levels, the ion pumps cannot function resulting in a rise in Ca2+ which further consumes ATP (Farber and Gerson 1984; Jennings et al. 1990; Jennings and Reimer 1981; Jennings and Steenbergen 1985). The rise in Ca2+ during ischemia and reperfusion leads to mitochondrial Ca2+ accumulation, particularly during reperfusion when oxygen is reintroduced. Reintroduction of oxygen provides a terminal electron acceptor (oxygen) allowing electron transport to occur; however damage to electron transport chain can lead to increased mitochondrial generation of reactive oxygen species (ROS).
KeywordsMitochondrial Membrane Potential Mitochondrial Permeability Transition Pore Voltage Dependent Anion Channel Adenine Nucleotide Translocator mPTP Opening
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- Baines CP, Zhang J, Wang GW, Zheng YT, Xiu JX, Cardwell EM, Bolli R, Ping P (2002) Mitochondrial PKCepsilon and MAPK form signaling modules in the murine heart: enhanced mitochondrial PKCepsilon-MAPK interactions and differential MAPK activation in PKCepsilon-induced cardioprotection. Circ Res 90: 390–397CrossRefPubMedGoogle Scholar
- Boengler K, Dodoni G, Rodriguez-Sinovas A, Cabestrero A, Ruiz-Meana M, Gres P, Konietzka I, Lopez-Iglesias C, Garcia-Dorado D, Di Lisa F, Heusch G, Schulz R (2005) Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res 67: 234–244CrossRefPubMedGoogle Scholar
- Jennings RB, Ganote CE (1976) Mitochondrial structure and function in acute myocardial ischemic injury. Circ Res 38: I80–91Google Scholar
- Juhaszova M, Zorov DB, Kim SH, Pepe S, Fu Q, Fishbein KW, Ziman BD, Wang S, Ytrehus K, Antos CL, Olson EN, Sollott SJ (2004) Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113: 1535–1549PubMedGoogle Scholar
- Kuznetsov AV, Schneeberger S, Seiler R, Brandacher G, Mark W, Steurer W, Saks V, Usson Y, Margreiter R, Gnaiger E (2004) Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion. Am J Physiol Heart Circ Physiol 286: H1633–1641CrossRefPubMedGoogle Scholar
- Schneider MD (2005) Cyclophilin D: knocking on death’s door. Sci STKE 2005 pe26Google Scholar