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

Lei Liu, Du Feng, Guo Chen, Ming Chen, Qiaoxia Zheng, Pingping Song, Qi Ma, Chongzhuo Zhu, Rui Wang, Wanjun Qi, Lei Huang, Peng Xue, Baowei Li, Xiaohui Wang, Haijing Jin, Jun Wang, Fuquan Yang, Pingsheng Liu, Yushan Zhu, Senfang SuiQuan Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

704 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalNature Cell Biology
Volume14
Issue number2
DOIs
StatePublished - Feb 2012
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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