ULK1 Translocates to Mitochondria and Phosphorylates FUNDC1 to Regulate Mitophagy

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2014 Mar 28

PMID 24671035

Citations 289

Authors

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

Affiliations

Soon will be listed here.

Abstract

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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