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CHK2 Promotes Metabolic Stress-Induced Autophagy through ULK1 Phosphorylation

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 in...

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Autores principales: Guo, Ran, Wang, Shan-Shan, Jiang, Xiao-You, Zhang, Ye, Guo, Yang, Cui, Hong-Yan, Guo, Qi-Qiang, Cao, Liu, Xie, Xiao-Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219861/
https://www.ncbi.nlm.nih.gov/pubmed/35740063
http://dx.doi.org/10.3390/antiox11061166
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author Guo, Ran
Wang, Shan-Shan
Jiang, Xiao-You
Zhang, Ye
Guo, Yang
Cui, Hong-Yan
Guo, Qi-Qiang
Cao, Liu
Xie, Xiao-Chen
author_facet Guo, Ran
Wang, Shan-Shan
Jiang, Xiao-You
Zhang, Ye
Guo, Yang
Cui, Hong-Yan
Guo, Qi-Qiang
Cao, Liu
Xie, Xiao-Chen
author_sort Guo, Ran
collection PubMed
description 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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spelling pubmed-92198612022-06-24 CHK2 Promotes Metabolic Stress-Induced Autophagy through ULK1 Phosphorylation Guo, Ran Wang, Shan-Shan Jiang, Xiao-You Zhang, Ye Guo, Yang Cui, Hong-Yan Guo, Qi-Qiang Cao, Liu Xie, Xiao-Chen Antioxidants (Basel) Article 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. MDPI 2022-06-14 /pmc/articles/PMC9219861/ /pubmed/35740063 http://dx.doi.org/10.3390/antiox11061166 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guo, Ran
Wang, Shan-Shan
Jiang, Xiao-You
Zhang, Ye
Guo, Yang
Cui, Hong-Yan
Guo, Qi-Qiang
Cao, Liu
Xie, Xiao-Chen
CHK2 Promotes Metabolic Stress-Induced Autophagy through ULK1 Phosphorylation
title CHK2 Promotes Metabolic Stress-Induced Autophagy through ULK1 Phosphorylation
title_full CHK2 Promotes Metabolic Stress-Induced Autophagy through ULK1 Phosphorylation
title_fullStr CHK2 Promotes Metabolic Stress-Induced Autophagy through ULK1 Phosphorylation
title_full_unstemmed CHK2 Promotes Metabolic Stress-Induced Autophagy through ULK1 Phosphorylation
title_short CHK2 Promotes Metabolic Stress-Induced Autophagy through ULK1 Phosphorylation
title_sort chk2 promotes metabolic stress-induced autophagy through ulk1 phosphorylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219861/
https://www.ncbi.nlm.nih.gov/pubmed/35740063
http://dx.doi.org/10.3390/antiox11061166
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