Mitochondrial association of alpha-synuclein causes oxidative stress

被引：258
|
作者：
Parihar, M. S.
Parihar, A.
Fujita, M. [1 ]
Hashimoto, M. [1 ]
Ghafourifar, P.
机构：
[1] Tokyo Metropolitan Inst Neurosci, Lab Chem & Metab, Tokyo, Japan
来源：
CELLULAR AND MOLECULAR LIFE SCIENCES | 2008年 / 65卷 / 7-8期
关键词：
alpha synuclein; mitochondria; nitric oxide; Parkinson's disease; mitochondrial calcium; cytochrome c; mitochondrial nitric oxide synthase; oxidative stress;
D O I：
10.1007/s00018-008-7589-1
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：1272 / 1284
页数：13
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