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 (DeltaPsi(M)) contributes to MPP(+)-induced apoptosis. The reduction in DeltaPsi(M) appears to result from decreased proton pumping at complex I and therefore decreased complex I activity may also contribute to apoptosis in PD.
Tatton
W G
WG
Department of Neurology, Mount Sinai School of Medicine, Annenburg 1470, P.O. Box 1137, One Gustave L. Levy Place, New York, NY, 10029-6574, USA.
Chalmers-Redman
R M
RM
Rideout
H J
HJ
Tatton
N A
NA