4.7 Article

Parkinson's disease-associated pathogenic VPS35 mutation causes complex I deficits

期刊

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2017.07.032

关键词

Parkinson's disease; Mitochondrial fission; VPS35; Complex I deficits; Blue native gel electrophoresis

资金

  1. NIH [NS083385, NS083498]
  2. Chinese Overseas, Hong Kong and Macao Scholars Collaborated Research Fund [81228007]
  3. Dr. Robert M. Kohrman Memorial Fund
  4. National Natural Science Foundation of China [81471287, 81071024, 81171202, 81371407, 30872729, 30870879]
  5. Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant [20152201]

向作者/读者索取更多资源

Defect in the complex I of the mitochondrial electron-transport chain is a characteristic of Parkinson's disease (PD) which is thought to play a critical role in the disease pathogenesis. Mutations in vacuolar protein sorting 35 (VPS35) cause autosomal dominant PD and we recently demonstrated that pathogenic VPS35 mutations cause mitochondrial damage through enhanced mitochondrial fragmentation. In this study, we aimed to determine whether pathogenic VPS35 mutation impacts the activity of complex I and its underlying mechanism. Indeed, VPS35 D620N mutation led to decreased enzymatic activity and respiratory defects in complex I and II in patient fibroblasts. While no changes in the expression of the complex I and II subunits were noted, the level of assembled complex I and II as well as the supercomplex was significantly reduced in D620N fibroblasts. Importantly, inhibition of mitochondrial fission rescued the contents of assembled complexes as well as the functional defects in complex I and II. Overall, these results suggest that VPS35 D620N mutation-induced excessive mitochondrial fission leads to the defects in the assembled complex I and supercomplex and causes bioenergetics deficits.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据