The mitochondrial permeability transition pore: its fundamental role in mediating cell death during ischaemia and reperfusion

It is widely acknowledged that apoptosis contributes to cell death associated with ischaemia-reperfusion injury. However, the mechanism surrounding its induction is controversial, with a few studies showing apoptosis induced by ischaemia alone [ [1] Fliss H. Gattinger D. Apoptosis in ischaemic and reperfused rat myocardium. Circ Res. 1996; 79: 949-956 Crossref PubMed Scopus (772) Google Scholar ], whereas the majority of studies reporting apoptosis induced by ischaemia when followed by a period of reperfusion [ 1 Fliss H. Gattinger D. Apoptosis in ischaemic and reperfused rat myocardium. Circ Res. 1996; 79: 949-956 Crossref PubMed Scopus (772) Google Scholar , 2 Gottlieb R.A. Burleson K.O. Kloner R.A. Babior B.M. Engler R.L. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest. 1994; 94: 1621-1628 Crossref PubMed Scopus (1346) Google Scholar , 3 Scarabelli T.M. Knight R.A. Rayment N.B. Cooper T.J. Stephanou A. Brar B.K. et al. Quantitative assessment of cardiac myocyte apoptosis in tissue sections using the fluorescence-based TUNEL technique enhanced with counterstains. J Immunol Meth. 1999; 228: 23-28 Crossref PubMed Scopus (49) Google Scholar , 4 Zhao Z.Q. Nakamura M. Wang N.P. Wilcox J.N. Shearer S. Ronson R.S. et al. Reperfusion induces myocardial apoptotic cell death. Cardiovasc Res. 2000; 45: 651-660 Crossref PubMed Scopus (254) Google Scholar ]. Since apoptosis is an energy-dependent process, it has been postulated that apoptosis requires a period of reperfusion to generate the necessary ATP required for it to proceed [ [4] Zhao Z.Q. Nakamura M. Wang N.P. Wilcox J.N. Shearer S. Ronson R.S. et al. Reperfusion induces myocardial apoptotic cell death. Cardiovasc Res. 2000; 45: 651-660 Crossref PubMed Scopus (254) Google Scholar ].