ON THE INVOLVEMENT OF A MITOCHONDRIAL PORE IN REPERFUSION INJURY

We review evidence implicating mitochondrial dysfunction in the pathog enesis of ischaemia/reperfusion injury. The lesion has been identified as a non selective pore that is triggered by Ca2+ and particular meta bolic derangements associated with this form of injury, namely falling ATP, raised P(i) and oxidative stress. Once activated, the pore flick ers between open and closed states and disrupts mitochondrial energy t ransduction, allowing ATP hydrolysis by the F(I)F(o) ATPase. Pore acti vation is prevented by cyclosporin A, which also retards the onset of necrosis in heart cells subjected to substrate-free anoxia and allows partial regeneration of ATP on reoyxgenation.