Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells

被引：1604

作者：

Liu, Lei ^{[1
,2
]}

Feng, Du ^{[3
]}

Chen, Guo ^{[3
]}

Chen, Ming ^{[1
,2
]}

Zheng, Qiaoxia ^{[1
,2
]}

Song, Pingping ^{[3
]}

Ma, Qi ^{[1
,2
]}

Zhu, Chongzhuo ^{[1
,2
]}

Wang, Rui ^{[1
]}

Qi, Wanjun ^{[3
]}

Huang, Lei ^{[4
,5
]}

Xue, Peng ^{[6
]}

Li, Baowei ^{[1
,2
]}

Wang, Xiaohui ^{[1
]}

Jin, Haijing ^{[1
]}

Wang, Jun ^{[1
]}

Yang, Fuquan ^{[6
]}

Liu, Pingsheng ^{[2
]}

Zhu, Yushan ^{[3
]}

Sui, Senfang ^{[4
]}

Chen, Quan ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China

[2] Chinese Acad Sci, Grad Sch, Beijing 100101, Peoples R China

[3] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China

[4] Tsinghua Univ, Coll Life Sci, Beijing 100084, Peoples R China

[5] Tsinghua Univ, Ctr Biomed Anal, Beijing 100084, Peoples R China

[6] Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China

来源：

NATURE CELL BIOLOGY | 2012年 / 14卷 / 02期

基金：

中国国家自然科学基金;

关键词：

PHOSPHORYLATION SITES; OXIDATIVE STRESS; AUTOPHAGY; PARKIN; ATG32; SRC; DEGRADATION; DYSFUNCTION; P62/SQSTM1; MATURATION;

D O I：

10.1038/ncb2422

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Accumulating evidence has shown that dysfunctional mitochondria can be selectively removed by mitophagy. Dysregulation of mitophagy is implicated in the development of neurodegenerative disease and metabolic disorders. How individual mitochondria are recognized for removal and how this process is regulated remain poorly understood. Here we report that FUNDC1, an integral mitochondrial outer-membrane protein, is a receptor for hypoxia-induced mitophagy. FUNDC1 interacted with LC3 through its typical LC3-binding motif Y(18)xxL(21), and mutation of the LC3-interaction region impaired its interaction with LC3 and the subsequent induction of mitophagy. Knockdown of endogenous FUNDC1 significantly prevented hypoxia-induced mitophagy, which could be reversed by the expression of wild-type FUNDC1, but not LC3-interaction-deficient FUNDC1 mutants. Mechanistic studies further revealed that hypoxia induced dephosphorylation of FUNDC1 and enhanced its interaction with LC3 for selective mitophagy. Our findings thus offer insights into mitochondrial quality control in mammalian cells.

引用

页码：177 / 185

页数：9

共 40 条

[1]

Phosphorylation of Serine 114 on Atg32 mediates mitophagy [J].