| Literature DB >> 25980607 |
Weili Tian1, Wen Li1, Yinqin Chen2, Zeming Yan3, Xia Huang4, Haixia Zhuang4, Wangtao Zhong1, Yusen Chen1, Wenxian Wu1, Chunxia Lin1, Hao Chen1, Xiaoyan Hou1, Liangqing Zhang4, Senfang Sui5, Bin Zhao1, Zhe Hu6, Longxuan Li7, Du Feng8.
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.Entities:
Keywords: Adenosine 5′-monophosphate (AMP)-activated protein kinase; Autophagy; Hypoxia; Mitochondria; Mitophagy; UNC-51 like kinase
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Year: 2015 PMID： 25980607 DOI： 10.1016/j.febslet.2015.05.020
Source DB: PubMed Journal: FEBS Lett ISSN： 0014-5793 Impact factor: 4.124