Mitochondrial association of alpha-synuclein causes oxidative stress |
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| Authors: | M S Parihar A Parihar M Fujita M Hashimoto P Ghafourifar |
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| Institution: | (1) Department of Surgery, Davis Heart and Lung Research Institute, and Institute of Mitochondrial Biology, Ohio State University, 460 West 12th Avenue, Columbus, 43210, OH, USA;(2) Laboratory for Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan |
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| Abstract: | α-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 α-synuclein with mitochondria and
consequences of such interaction. Using SHSY cells overexpressing α-synuclein A53T mutant or wild-type, as well as isolated
rat brain mitochondria, the present study shows that α-synuclein localizes at the mitochondrial membrane. In both SHSY cells
and isolated mitochondria, interaction of α-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 α-synuclein.
Received 27 December 2007; received after revision 7 February 2008; accepted 8 February 2008 |
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| Keywords: | Alpha synuclein mitochondria nitric oxide Parkinson’ s disease mitochondrial calcium cytochrome c mitochondrial nitric oxide synthase oxidative stress |
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