α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson's disease

被引:89
作者
Banerjee, Kalpita [1 ]
Sinha, Maitrayee [1 ]
Pham, Chi Le Lan [2 ,3 ]
Jana, Sirsendu [1 ]
Chanda, Dalia [1 ]
Cappai, Roberto [2 ,3 ]
Chakrabarti, Sasanka [1 ]
机构
[1] Postgrad Inst Med Educ & Res, Dept Biochem, Kolkata 700020, India
[2] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia
[3] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia
基金
英国医学研究理事会;
关键词
alpha-Synuclein; Dopamine; Parkinson's disease; Mitochondria; Membrane potential; Phosphorylation; DOPAMINE; AGGREGATION;
D O I
10.1016/j.febslet.2010.03.012
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
This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human alpha-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, alpha-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting that the former may impair mitochondrial bioenergetics by direct effect on mitochondrial membranes. Moreover, the recombinant wild type alpha-synuclein and different mutant forms (A30P, A53T and E46K) have essentially similar effects on rat brain isolated mitochondria. The results are significant in view of the fact that alpha-synucleinopathy is involved in the pathogenesis of Parkinson's disease. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:1571 / 1576
页数:6
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