Molecular pathways of programmed cell death in experimental Parkinson's disease.
Dysfunction of mitochondrial complex I leads to degeneration of dopaminergic neurons of the substantia nigra pars compacta, as seen in Parkinson's disease, through activation of mitochondria-dependent programmed cell death pathways. In this scenario, complex I blockade increases the soluble pool of cytochrome c in the mitochondrial intermembrane space through oxidative mechanisms, whereas activation of pro-cell death protein Bax triggers neuronal death by permeabilizing the outer mitochondrial membrane and releasing cytochrome c into the cytosol. Targeting either Bax transcriptional or post-translational activation results in a marked attenuation of dopaminergic cell death caused by complex I inhibition.
Vila
Miquel
M
Catalan Institution for Research and Advanced Studies, Barcelona, Spain. mvila@it.vhebron.net
Perier
Celine
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
D042967:Electron Transport Complex I