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Cell Mol Life Sci. 2008 Apr;65(7-8):1272-84. doi: 10.1007/s00018-008-7589-1.

Mitochondrial association of alpha-synuclein causes oxidative stress.

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  • 1Department of Surgery, Davis Heart and Lung Research Institute, Ohio State University, 460 West 12th Avenue, Columbus, 43210 OH, USA.

Abstract

Alpha-synuclein is a neuron-specific protein that contributes to the pathology of Parkinson's disease via mitochondria-related mechanisms. The present study investigated possible interaction of alpha-synuclein with mitochondria and consequences of such interaction. Using SHSY cells overexpressing alpha-synuclein A53T mutant or wild-type, as well as isolated rat brain mitochondria, the present study shows that alpha-synuclein localizes at the mitochondrial membrane. In both SHSY cells and isolated mitochondria, interaction of alpha-synuclein with mitochondria causes release of cytochrome c, increase of mitochondrial calcium and nitric oxide, and oxidative modification of mitochondrial components. These findings suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by alpha-synuclein.

PMID:
18322646
DOI:
10.1007/s00018-008-7589-1
[PubMed - indexed for MEDLINE]
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