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ULK 1 translocates to mitochondria and phosphorylates FUNDC 1 to regulate mitophagy
Author(s) -
Wu Wenxian,
Tian Weili,
Hu Zhe,
Chen Guo,
Huang Lei,
Li Wen,
Zhang Xingli,
Xue Peng,
Zhou Changqian,
Liu Lei,
Zhu Yushan,
Zhang Xingliang,
Li Longxuan,
Zhang Liangqing,
Sui Senfang,
Zhao Bin,
Feng Du
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1002/embr.201438501
Subject(s) - mitophagy , microbiology and biotechnology , phosphorylation , mitochondrion , chemistry , biology , autophagy , biochemistry , apoptosis
Autophagy eliminates dysfunctional mitochondria in an intricate process known as mitophagy. ULK 1 is critical for the induction of autophagy, but its substrate(s) and mechanism of action in mitophagy remain unclear. Here, we show that ULK 1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK 1 interacts with FUNDC 1, phosphorylating it at serine 17, which enhances FUNDC 1 binding to LC 3. A ULK 1‐binding‐deficient mutant of FUNDC 1 prevents ULK 1 translocation to mitochondria and inhibits mitophagy. Finally, kinase‐active ULK 1 and a phospho‐mimicking mutant of FUNDC 1 rescue mitophagy in ULK 1‐null cells. Thus, we conclude that FUNDC 1 regulates ULK 1 recruitment to damaged mitochondria, where FUNDC 1 phosphorylation by ULK 1 is crucial for mitophagy.