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MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease.
Lin, Meng; Xian, Huifang; Chen, Zhanghua; Wang, Shang; Liu, Ming; Liang, Weiwei; Tang, Qin; Liu, Yao; Huang, Wanming; Che, Di; Guo, Caiqin; Idiiatullina, Elina; Fang, Rongli; Al-Azab, Mahmoud; Chang, Jingjie; Wang, Rongze; Li, Xiaojun; Zuo, Xiaoyu; Zhang, Yan; Zhao, Jincun; Tang, Yaping; Jin, Shouheng; He, Zhengjie; Feng, Du; Lu, Liwei; Zhang, Kang; Wu, Yan; Bai, Fan; Lew, Andrew M; Cui, Jun; Wu, Yuzhang; Gu, Xiaoqiong; Zhang, Yuxia.
Afiliação
  • Lin M; 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.
  • Xian H; Pediatric Immunity and Healthcare Biomedical Co., Ltd, Guangzhou, China.
  • Chen Z; 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.
  • Wang S; 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.
  • Liu M; 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.
  • Liang W; 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.
  • Tang Q; 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.
  • Liu Y; 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.
  • Huang W; 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.
  • Che D; 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.
  • Guo C; 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.
  • Idiiatullina E; 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.
  • Fang R; 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.
  • Al-Azab M; 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.
  • Chang J; 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.
  • Wang R; 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.
  • Li X; 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.
  • Zuo X; 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.
  • Zhang Y; 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.
  • Zhao J; 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.
  • Tang Y; 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.
  • Jin S; 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.
  • He Z; MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Feng D; Guangzhou 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.
  • Lu L; Guangzhou 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.
  • Zhang K; Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China.
  • Wu Y; Chongqing International Institute for Immunology, Chongqing, China.
  • Bai F; Guangzhou National Laboratory, Guangzhou, China.
  • Lew AM; Department of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Cui J; Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing, China.
  • Wu Y; Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
  • Gu X; MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Zhang Y; Chongqing International Institute for Immunology, Chongqing, China. wuyuzhang@iiicq.vip.
Nat Cardiovasc Res ; 2(8): 778-792, 2023 Aug.
Article em En | MEDLINE | ID: mdl-39195969
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Modelos Animais de Doenças / Mitofagia / Síndrome de Linfonodos Mucocutâneos / Óxido Nítrico Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Modelos Animais de Doenças / Mitofagia / Síndrome de Linfonodos Mucocutâneos / Óxido Nítrico Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article