Document Detail

ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy.
MedLine Citation:
PMID:  24671035     Owner:  NLM     Status:  Publisher    
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.
Wenxian Wu; Weili Tian; Zhe Hu; Guo Chen; Lei Huang; Wen Li; Xingli Zhang; Peng Xue; Changqian Zhou; Lei Liu; Yushan Zhu; Xingliang Zhang; Longxuan Li; Liangqing Zhang; Senfang Sui; Bin Zhao; Du Feng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-3-26
Journal Detail:
Title:  EMBO reports     Volume:  -     ISSN:  1469-3178     ISO Abbreviation:  EMBO Rep.     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-3-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100963049     Medline TA:  EMBO Rep     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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