4.7 Article

CHK2 Promotes Metabolic Stress-Induced Autophagy through ULK1 Phosphorylation

期刊

ANTIOXIDANTS
卷 11, 期 6, 页码 -

出版社

MDPI
DOI: 10.3390/antiox11061166

关键词

autophagy; ULK1; CHK2; oxidative stress; ROS

资金

  1. National Key R&D Program of China [2016YFC1302400]
  2. Key projects of the National Natural Fund of China [82030091]
  3. Natural Science Foundation of China [81702738, 81073089, 81502400]
  4. Ministry of Education Innovation Team Development Plan [IRT13101/17R107]
  5. Scientific research project of Liaoning Provincial Department of Education [JC2019016, JC2019039]

向作者/读者索取更多资源

This study reveals that reactive oxygen species (ROS) initiate autophagy through the ATM/CHK2/ULK1 axis to maintain cellular homeostasis and protect cells from metabolic stress-induced damage.
Reactive oxygen species (ROS) act as a signaling intermediate to promote cellular adaptation to maintain homeostasis by regulating autophagy during pathophysiological stress. However, the mechanism by which ROS promotes autophagy is still largely unknown. Here, we show that the ATM/CHK2/ULK1 axis initiates autophagy to maintain cellular homeostasis by sensing ROS signaling under metabolic stress. We report that ULK1 is a physiological substrate of CHK2, and that the binding of CHK2 to ULK1 depends on the ROS signal and the phosphorylation of threonine 68 of CHK2 under metabolic stress. Further, CHK2 phosphorylates ULK1 on serine 556, and this phosphorylation is dependent on the ATM/CHK2 signaling pathway. CHK2-mediated phosphorylation of ULK1 promotes autophagic flux and inhibits apoptosis induced by metabolic stress. Taken together, these results demonstrate that the ATM/CHK2/ULK1 axis initiates an autophagic adaptive response by sensing ROS, and it protects cells from metabolic stress-induced cellular damage.

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