Mitochondrial permeability in neuronal death: possible relevance to the pathogenesis of Parkinson' s disease

1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) causes catecholaminergic nerve cell loss and a syndrome similar to Parkinson's disease (PD). The metabolite of MPTP, MPP+ (1-methyl-4-phenylpyridinium), decreases mitochondrial complex I activity similar to that in the PD nigra. Opening of a multi-protein, mitochondrial membrane pore constitutes a critical decisional event in some forms of apoptosis. We review recent findings showing that the permeability transition pore (PTP) opening caused by a decrease in the mitochondrial membrane potential (Delta Psi(M)) contributes to MPP+-induced apoptosis. The reduction in Delta Psi(M) appears to result from decreased proton pumping at complex I and therefore decreased complex I activity may also contribute to apoptosis in PD, (C) 1999 Elsevier Science Ltd. All rights reserved.