The mitochondrial permeability transition pore and its role in cell death

Abstract

This article reviews the involvement of the mitochondrial permeability transition pore in necrotic and apoptotic cell death.The pore is formed from a complex of the voltage-dependent anion channel (VDAC), the adenine nucleotide translocase and cyclophilin-D (CyP-D) at contact sites between the mitochondrial outer and inner membranes.In itro, under pseudopathological conditions of oxidative stress, relatively high Ca# + and low ATP, the complex flickers into an open-pore state allowing free diffusion of low-M r solutes across the inner membrane.These conditions correspond to those that unfold during tissue ischaemia and reperfusion, suggesting that pore opening may be an important factor in the pathogenesis of necrotic cell death following ischaemia\reperfusion.Evidence that the pore does open during ischaemia\reperfusion is discussed.There are also 1 Ca 2 + CYCLING AND THE CONTROL OF MITOCHONDRIAL Ca 2 + PT-induced mitochondrial dysfunction is a consequence of mitochondrial Ca# + overload.It is appropriate, therefore, to define the conditions under which the overload takes place.In the following, mitochondrial Ca# + overload is discussed against a background of how mitochondrial Ca# + is controlled normally, and how it can lead to PT pore opening.