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IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.
Brunetta, Henver S; Jung, Anna S; Valdivieso-Rivera, Fernando; de Campos Zani, Stepheny C; Guerra, Joel; Furino, Vanessa O; Francisco, Annelise; Berçot, Marcelo; Moraes-Vieira, Pedro M; Keipert, Susanne; Jastroch, Martin; Martinez, Laurent O; Sponton, Carlos H; Castilho, Roger F; Mori, Marcelo A; Bartelt, Alexander.
Afiliação
  • Brunetta HS; Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil.
  • Jung AS; Institute for Cardiovascular Prevention (IPEK), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
  • Valdivieso-Rivera F; Institute for Cardiovascular Prevention (IPEK), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
  • de Campos Zani SC; Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.
  • Guerra J; Obesity and Comorbidities Research Center (OCRC), University of Campinas, Campinas, SP, Brazil.
  • Furino VO; Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil.
  • Francisco A; Institute for Cardiovascular Prevention (IPEK), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
  • Berçot M; Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.
  • Moraes-Vieira PM; Obesity and Comorbidities Research Center (OCRC), University of Campinas, Campinas, SP, Brazil.
  • Keipert S; Department of Pathology, University of Campinas, Campinas, SP, Brazil.
  • Jastroch M; Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas, Campinas, SP, Brazil.
  • Martinez LO; Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas, Campinas, SP, Brazil.
  • Sponton CH; Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas, SP, Brazil.
  • Castilho RF; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
  • Mori MA; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
  • Bartelt A; LiMitAging Team, Institute of Metabolic and Cardiovascular Diseases, I2MC UMR1297, IHU HealthAge, INSERM, University of Toulouse, Université Toulouse III - Paul Sabatier (UPS), Toulouse, France.
EMBO J ; 2024 Sep 16.
Article em En | MEDLINE | ID: mdl-39284909
ABSTRACT
While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether F1Fo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called "reverse mode" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: EMBO J Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: EMBO J Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido