On the involvement of a mitochondrial pore in reperfusion injury

We review evidence implicating mitochondrial dysfunction in the pathogenesis of ischaemia/reperfusion injury. The lesion has been identified as a non selective pore that is triggered by Ca2+ and particular metabolic derangements associated with this form of injury, namely falling ATP, raised Pi and oxidative stress. Once activated, the pore flickers between open and closed states and disrupts mitochondrial energy transduction, allowing ATP hydrolysis by the F1F0 ATPase. Pore activation 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 reoxygenation.