ArticleNature cardiovascular research2023
MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease.
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Article in Nature cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- The Autophagy-Inflammasome Axis as a Molecular Switch: From Persistent Inflammation to Vascular Remodeling in IVIG-Resistant Kawasaki Disease.International journal of molecular sciences · 2026Review
- Rational design of carbazole-based STING inhibitors for treating cGAS-STING pathway-driven inflammatory disorders.Nature communications · 2026Article
- The Autophagy-Inflammation Axis in Kawasaki Disease: Pathogenic Mechanisms and Translational Opportunities.Journal of clinical medicine · 2026Review
- Estrogen deprivation induces hepatic inflammation, Indoleamine-2,3-dioxygenase 1, tryptophan catabolism, and plasma cholesterol.Scientific reports · 2026Article
- Sustained nitric oxide production by engineered E. coli remodels the tumor microenvironment and potentiates immunotherapy.Nature biotechnology · 2026Article
- Superoxide signals for the mitophagy of dysfunctional mitochondria to maintain quality control.Redox biology · 2026Review
- Periodontitis and cardiovascular diseases: bridging the gap through mitochondrial dysfunction.Frontiers in oral health · 2026Review
- Multifaceted role of nitric oxide in vascular dementia.Medical gas research · 2025Review
- Double-edged mitophagy: balancing inflammation and resolution in lung disease.Clinical science (London, England : 1979) · 2025Review
- Mitochondrial homeostasis restoring peptide-drug conjugates with ROS-responsive NO releasing ability for targeted therapy of myocardial infarction.Journal of nanobiotechnology · 2025Article
- Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model.Frontiers in cell and developmental biology · 2025Article
- Targeting selective autophagy and beyond: From underlying mechanisms to potential therapies.Journal of advanced research · 2024Review
- Identification of novel mitophagy-related biomarkers for Kawasaki disease by integrated bioinformatics and machine-learning algorithms.Translational pediatrics · 2024Article
- Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases.Frontiers in pharmacology · 2024Review
- Mitophagy in hypertension-mediated organ damage.Frontiers in cardiovascular medicine · 2023Review
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Authors and funding
33 authors.
Meng Lin *Clinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Huifang Xian *Clinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Zhanghua Chen *Clinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-2505-0675
Shang Wang *Clinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Ming LiuClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Weiwei LiangClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Qin TangClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Yao LiuClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Wanming HuangClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Di CheClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Caiqin GuoClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Elina IdiiatullinaClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0001-5324-2896
Rongli FangClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Mahmoud Al-AzabClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Jingjie ChangClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-3191-6746
Rongze WangClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Xiaojun LiClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Xiaoyu ZuoClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Yan ZhangClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Jincun ZhaoClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0003-2515-5589
Yaping TangClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-0445-4072
Shouheng JinMOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.ORCID 0000-0002-2728-2859
Zhengjie HeGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0003-1900-0249
Du FengGuangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-2489-4702
Liwei LuDepartment of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China.ORCID 0000-0002-8634-0967
Kang ZhangGuangzhou National Laboratory, Guangzhou, China.ORCID 0000-0002-4549-1697
Yan WuDepartment of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Fan BaiBiomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing, China.ORCID 0000-0001-6119-8936
Andrew M LewWalter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
Jun CuiMOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.ORCID 0000-0002-8000-3708
Yuzhang WuChongqing International Institute for Immunology, Chongqing, China. wuyuzhang@iiicq.vip.ORCID 0000-0002-4049-0214
Xiaoqiong GuClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China. guxiaoqiong@gwcmc.org.ORCID 0000-0002-9558-4226
Yuxia ZhangClinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China. yuxia.zhang@gwcmc.org.ORCID 0000-0003-2715-0925
Funding
National Natural Science Foundation of China (National Science Foundation of China) 32100735National Natural Science Foundation of China (National Science Foundation of China) 81901665National Natural Science Foundation of China (National Science Foundation of China) 82125015,92042303
Abstract
Mitophagy is a major quality control pathway that removes unwanted or dysfunctional mitochondria and plays an essential role in vascular health. Here we show that MCM8 expression is significantly decreased in children with Kawasaki disease (KD) who developed coronary artery aneurysms. Mechanistically, we discovered that nitric oxide signaling promotes TRIM21-mediated MCM8 ubiquitination, which disrupts its interaction with MCM9 and promotes its cytosolic export. In the cytosol, MCM8 relocates to the mitochondria pore-forming proteins and promotes their ubiquitination by TRIM21. In addition, MCM8 directly recruits LC3 via its LC3-interacting region (LIR) motif and initiates mitophagy. This suppresses mitochondrial DNA-mediated activation of type I interferon via cGAS and STING. Mice that are deficient in Mcm8, Trim21 and Nos2 or reconstituted with the East-Asian-specific MCM8-P276 variant develop more severe coronary artery vasculopathy in the Lactobacillus casei extract-induced KD model. Collectively, the data suggest that MCM8 protects vascular health in the KD setting.
Indexed as
Disease Models, AnimalMitophagyMucocutaneous Lymph Node SyndromeNitric OxideSignal TransductionAnimalsCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseFemaleHumansMaleMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMinichromosome Maintenance ProteinsNucleotidyltransferasescGAS protein, humancGAS protein, mouseCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseMcm8 protein, mouseMembrane ProteinsMinichromosome Maintenance ProteinsNitric OxideNucleotidyltransferasesSting1 protein, mouseSTING Protein
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PMID
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