Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 65, Issue 7-8, Pages 1272-1284Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-008-7589-1
Keywords
alpha synuclein; mitochondria; nitric oxide; Parkinson's disease; mitochondrial calcium; cytochrome c; mitochondrial nitric oxide synthase; oxidative stress
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Funding
- NIA NIH HHS [AG 023264-02] Funding Source: Medline
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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.
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