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Proteolytic rewiring of mitochondria by LONP1 directs cell identity switching of adipocytes.
Fu, Tingting; Sun, Wanping; Xue, Jiachen; Zhou, Zheng; Wang, Wen; Guo, Qiqi; Chen, Xinyi; Zhou, Danxia; Xu, Zhisheng; Liu, Lin; Xiao, Liwei; Mao, Yan; Yang, Likun; Yin, Yujing; Zhang, Xue-Na; Wan, Qiangyou; Lu, Bin; Chen, Yuncong; Zhu, Min-Sheng; Scherer, Philipp E; Fang, Lei; Piao, Hai-Long; Shao, Mengle; Gan, Zhenji.
Afiliação
  • Fu T; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Sun W; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Xue J; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Zhou Z; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Wang W; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
  • Guo Q; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Chen X; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Zhou D; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Xu Z; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Liu L; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Xiao L; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Mao Y; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Yang L; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Yin Y; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
  • Zhang XN; State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing University, Nanjing, China.
  • Wan Q; CAS Key Laboratory of Molecular Virology and Immunology, The Center for Microbes, Development and Health, Chinese Academy of Sciences, Shanghai, China.
  • Lu B; Hengyang Medical College, University of South China, Hengyang, China.
  • Chen Y; State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
  • Zhu MS; State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing University, Nanjing, China.
  • Scherer PE; Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Fang L; Jiangsu Key Laboratory of Molecular Medicine, Chemistry and Biomedicine Innovation Center (ChemBIC), Medical School of Nanjing University, Nanjing, China.
  • Piao HL; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
  • Shao M; CAS Key Laboratory of Molecular Virology and Immunology, The Center for Microbes, Development and Health, Chinese Academy of Sciences, Shanghai, China. mlshao@ips.ac.cn.
  • Gan Z; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Ch
Nat Cell Biol ; 25(6): 848-864, 2023 06.
Article em En | MEDLINE | ID: mdl-37217599
ABSTRACT
Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity and acting as both protein quality surveillance and regulatory enzymes by performing highly regulated proteolytic reactions. However, it remains unclear whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switching. Here we report that cold-responsive mitochondrial proteolysis is a prerequisite for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling. Thermogenic stimulation selectively promotes mitochondrial proteostasis in mature white adipocytes via the mitochondrial protease LONP1. Disruption of LONP1-dependent proteolysis substantially impairs cold- or ß3 adrenergic agonist-induced white-to-beige identity switching of mature adipocytes. Mechanistically, LONP1 selectively degrades succinate dehydrogenase complex iron sulfur subunit B and ensures adequate intracellular succinate levels. This alters the histone methylation status on thermogenic genes and thereby enables adipocyte cell fate programming. Finally, augmented LONP1 expression raises succinate levels and corrects ageing-related impairments in white-to-beige adipocyte conversion and adipocyte thermogenic capacity. Together, these findings reveal that LONP1 links proteolytic surveillance to mitochondrial metabolic rewiring and directs cell identity conversion during adipocyte thermogenic remodelling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adipócitos / Mitocôndrias Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adipócitos / Mitocôndrias Idioma: En Ano de publicação: 2023 Tipo de documento: Article