ArticleThe EMBO journal2020
ATM-CHK2-Beclin 1 axis promotes autophagy to maintain ROS homeostasis under oxidative stress.
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Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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79citing papers in PubMed
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79 citing papers in PubMed, 139 citations in OpenAlex.
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Mitophagy mitigates mitochondrial DNA-induced activation of cGAS-STING in autoimmune thyroiditis.Nature communications · 2026Article
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- Checkpoint kinase 2 coordinates autophagy activation and Aurora kinase A degradation to regulate primary cilia for cell invasion.Cell communication and signaling : CCS · 2026Article
- Chronic melamine cyanurate exposure impairs spatial learning and memory by altering autophagy-mediated synaptic plasticity and oxidative stress in the hippocampus of adolescent rats.Archives of toxicology · 2026Article
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- Targeting DNA Damage and Repair Pathways in Cerebral Ischemic Stroke: From Bench to Bedside.Translational stroke research · 2026Review
- Autophagy in ischemic stroke: pathophysiology, therapeutics, and challenges ahead.Frontiers in stroke · 2026Review
- From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review).Oncology reports · 2026Review
- Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- Mitochondrial ROS triggers mitophagy through activating the DNA damage response signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Biological Role and Clinical Significance of BECLIN-1 in Cancer.International journal of molecular sciences · 2025Review
- Basal autophagy during meiotic prophase I is required for accurate chromosome segregation inMolecular biology of the cell · 2025Article
- Oxidative Stress in the Regulation of Autosis-Related Proteins.Antioxidants (Basel, Switzerland) · 2025Review
- Targeting ATM enhances radiation sensitivity of colorectal cancer by potentiating radiation-induced cell death and antitumor immunity.Journal of advanced research · 2025Article
- DNA damage response pathway regulates Nrf2 in response to oxidative stress.Science advances · 2025Article
- The Crosstalk Between Ferritinophagy and Ferroptosis in Ischemic Stroke: Regulatory Mechanisms and Therapeutic Implications.Cellular and molecular neurobiology · 2025Review
- Activation of the MEK1-CHK2 axis in macrophages by Staphylococcus aureus promotes mitophagy, resulting in a reduction in bactericidal efficacy.Molecular medicine (Cambridge, Mass.) · 2025Article
- Re-epithelialization of cancer cells increases autophagy and DNA damage: Implications for breast cancer dormancy and relapse.Science signaling · 2025Article
- The link between ferroptosis and autophagy in myocardial ischemia/reperfusion injury: new directions for therapy.Journal of cardiovascular translational research · 2025Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 6 institutions in 2 countries.
Qi-Qiang GuoInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Shan-Shan WangInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Shan-Shan ZhangInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Hong-De XuInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Xiao-Man LiInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Yi GuanInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Fei YiInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Ting-Ting ZhouInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Bo JiangInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Ning BaiInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Meng-Tao MaInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Zhuo WangInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Yan-Ling FengInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Wen-Dong GuoInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Xuan WuInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.
Gui-Feng ZhaoDepartment of Experimental Oncology and Animal Center, Key Laboratory of Research and Application of Animal Models for Environmental and Metabolic Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
Guang-Jian FanInstitute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0003-0684-1380
Sheng-Ping ZhangInstitute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chuan-Gui WangInstitute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Long-Yue CaoWilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, NY, USA.
Brian P O'RourkeDepartment of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA.
Shi-Hui LiuAging Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Ping-Yuan WangCardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Shuai HanDepartment of Neurosurgery, The First Hospital of China medical University, Shenyang, China.ORCID 0000-0002-0398-2877
Xiao-Yu SongInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.ORCID 0000-0002-6606-327X
Liu CaoInstitute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.ORCID 0000-0001-6471-1993
China Medical University · CNShanghai Jiao Tong University · CNAlbert Einstein College of Medicine · USFirst Hospital of China Medical University · CNNational Institutes of Health · USUniversity of Pittsburgh · US
Funding
WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI THOMAS E ROHAN · 1985 to 2026
$111.2MMinistry of Education Innovation Team Development Plan IRT13101/17R107National Key R&D Program of China 2016YFC1302400National Natural Science Foundation of China (NSF) 31300963National Natural Science Foundation of China (NSF) 81502400National Natural Science Foundation of China (NSF) 81702738Natural Science Foundation of Liaoning Province (Liaoning Province Natural Science Foundation) L201571NCI NIH HHS P30 CA013330
Abstract
The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1-Bcl-2 autophagy-regulatory complex formation in a ROS-dependent fashion. We further demonstrate that CHK2-mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2
Indexed as
AnimalsAtaxia Telangiectasia Mutated ProteinsAutophagyBeclin-1Cell LineCheckpoint Kinase 2Disease Models, AnimalHCT116 CellsHEK293 CellsHeLa CellsHumansIschemic StrokeMiceOxidative StressPhosphorylationReactive Oxygen SpeciesAtaxia Telangiectasia Mutated ProteinsATM protein, humanBeclin-1BECN1 protein, humanCheckpoint Kinase 2CHEK2 protein, humanReactive Oxygen SpeciesautophagyBeclin 1CHK2oxidative stressROS
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.