Mitochondrial association of alpha-synuclein causes oxidative stress

作者：Parihar M S; Parihar A; Fujita M; Hashimoto M; Ghafourifar P^*

来源：Cellular and Molecular Life Sciences, 2008, 65(7-8): 1272-1284.

DOI：10.1007/s00018-008-7589-1

• alpha synuclein
• mitochondria
• nitric oxide
• Parkinson's disease
• mitochondrial calcium
• cytochrome c
• mitochondrial nitric oxide synthase
• oxidative stress

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.

• 出版日期2008-4