Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy

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 · 2015

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（腺苷）激活的蛋白激酶

期刊名称：

FEBS Letters 2015 年 589 卷 15 期

发表日期：

2015.07.03

摘要：

Abstract 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.