Journal
EMBO REPORTS
Volume 15, Issue 5, Pages 566-575Publisher
WILEY-BLACKWELL
DOI: 10.1002/embr.201438501
Keywords
ULK1; mitophagy; mitochondria; mitochondrial quality control; FUNDC1
Categories
Funding
- Guangdong Medical College [B2012043, B2012044, 701B01206]
- NSFC [31301104, 81171244]
- NSF of Guangdong province [S2011010004095]
- Ministry of Education for returning-back scholars of China [[2012]940]
- Foundation for Distinguished Young Talents in Higher Education of Guangdong, China [2013LYM_0035]
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Autophagy eliminates dysfunctional mitochondria in an intricate process known as mitophagy. ULK1 is critical for the induction of autophagy, but its substrate(s) and mechanism of action in mitophagy remain unclear. Here, we show that ULK1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 interacts with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to LC3. A ULK1-binding-deficient mutant of FUNDC1 prevents ULK1 translocation to mitochondria and inhibits mitophagy. Finally, kinase-active ULK1 and a phospho-mimicking mutant of FUNDC1 rescue mitophagy in ULK1-null cells. Thus, we conclude that FUNDC1 regulates ULK1 recruitment to damaged mitochondria, where FUNDC1 phosphorylation by ULK1 is crucial for mitophagy.
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