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ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue.
Kato, Hironori; Okabe, Kohki; Miyake, Masato; Hattori, Kazuki; Fukaya, Tomohiro; Tanimoto, Kousuke; Beini, Shi; Mizuguchi, Mariko; Torii, Satoru; Arakawa, Satoko; Ono, Masaya; Saito, Yusuke; Sugiyama, Takashi; Funatsu, Takashi; Sato, Katsuaki; Shimizu, Shigeomi; Oyadomari, Seiichi; Ichijo, Hidenori; Kadowaki, Hisae; Nishitoh, Hideki.
Afiliação
  • Kato H; Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan.
  • Okabe K; Laboratory of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
  • Miyake M; Division of Molecular Biology, Institute for Genome Research, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
  • Hattori K; Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
  • Fukaya T; Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Tanimoto K; Genome Laboratory, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
  • Beini S; Laboratory of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
  • Mizuguchi M; Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
  • Torii S; Department of Pathological Cell Biology, Medical Research Institute, TMDU, Tokyo, Japan.
  • Arakawa S; Department of Pathological Cell Biology, Medical Research Institute, TMDU, Tokyo, Japan.
  • Ono M; Department of Clinical Proteomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Saito Y; Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Sugiyama T; Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan.
  • Funatsu T; Laboratory of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
  • Sato K; Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Shimizu S; Department of Pathological Cell Biology, Medical Research Institute, TMDU, Tokyo, Japan.
  • Oyadomari S; Division of Molecular Biology, Institute for Genome Research, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
  • Ichijo H; Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
  • Kadowaki H; Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan.
  • Nishitoh H; Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan nishitoh@med.miyazaki-u.ac.jp.
Life Sci Alliance ; 3(3)2020 03.
Article em En | MEDLINE | ID: mdl-32029570
ABSTRACT
Mitochondria play a central role in the function of brown adipocytes (BAs). Although mitochondrial biogenesis, which is indispensable for thermogenesis, is regulated by coordination between nuclear DNA transcription and mitochondrial DNA transcription, the molecular mechanisms of mitochondrial development during BA differentiation are largely unknown. Here, we show the importance of the ER-resident sensor PKR-like ER kinase (PERK) in the mitochondrial thermogenesis of brown adipose tissue. During BA differentiation, PERK is physiologically phosphorylated independently of the ER stress. This PERK phosphorylation induces transcriptional activation by GA-binding protein transcription factor α subunit (GABPα), which is required for mitochondrial inner membrane protein biogenesis, and this novel role of PERK is involved in maintaining the body temperatures of mice during cold exposure. Our findings demonstrate that mitochondrial development regulated by the PERK-GABPα axis is indispensable for thermogenesis in brown adipose tissue.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tecido Adiposo Marrom / EIF-2 Quinase / Retículo Endoplasmático Limite: Animals Idioma: En Revista: Life Sci Alliance Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tecido Adiposo Marrom / EIF-2 Quinase / Retículo Endoplasmático Limite: Animals Idioma: En Revista: Life Sci Alliance Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Japão