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Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy
Author(s) -
Tian Weili,
Li Wen,
Chen Yinqin,
Yan Zeming,
Huang Xia,
Zhuang Haixia,
Zhong Wangtao,
Chen Yusen,
Wu Wenxian,
Lin Chunxia,
Chen Hao,
Hou Xiaoyan,
Zhang Liangqing,
Sui Senfang,
Zhao Bin,
Hu Zhe,
Li Longxuan,
Feng Du
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.05.020
Subject(s) - ulk1 , mitophagy , ampk , microbiology and biotechnology , autophagy , mitochondrion , protein kinase a , phosphorylation , chemistry , biology , biochemistry , apoptosis
UNC‐51 like kinase (ULK1) translocates to dysfunctional mitochondria and is involved in mitophagy, but the mechanisms responsible for ULK1 activation and translocation remain unclear. Here, we found that hypoxia induces phosphorylation of ULK1 at Serine‐555 by Adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK). Unlike wild‐type ULK1, an ULK1 (S555A) mutant cannot translocate to mitochondria in response to hypoxia. Inhibition or knockdown of AMPK prevents ULK1 translocation and inhibits mitophagy. Finally, the phospho‐mimic ULK1 (S555D) mutant, but not ULK1 (S555A), rescues mitophagy in AMPK‐knockdown cells. Thus, we conclude that AMPK‐dependent phosphorylation of ULK1 is critical for translocation of ULK1 to mitochondria and for mitophagy in response to hypoxic stress.