Mitochondrial association of alpha-synuclein causes oxidative stress

被引：257

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

页码：1272 / 1284

页数：13

共 66 条

[1] Expanding insights of mitochondrial dysfunction in Parkinson's disease [J].