Opposing action of NCoR1 and PGC-1 alpha in mitochondrial redox homeostasis

Autor(es):Mostrar menos -

Lima, Tanes I. ^{[1, 2, 3]} ; Guimaraes, Dimitrius Santiago P. S. F. ^{[1, 3]} ; Oliveira, Andre G. ^{[1, 3]} ; Araujo, Hygor ^{[1, 3]} ; Sponton, Carlos H. G. ^{[1, 3]} ; Souza-Pinto, Nadja C. ^[4] ; Saito, Angela ^[5] ; Figueira, Ana Carolina M. ^[5] ; Palameta, Soledad ^[5] ; Bajgelman, Marcio Chaim ^[5] ; Calixto, Andrea ^[6] ; Pinto, Silas ^[7] ; Mori, Marcelo A. ^[7] ; Orofino, Joey ^[8] ; Perissi, Valentina ^[8] ; Mottis, Adrienne ^[9] ; Auwerx, Johan ^[9] ; Silveira, Leonardo Reis ^{[1, 2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Dept Struct & Funct Biol, Inst Biol, Campinas, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP - Brazil

^[3] Univ Estadual Campinas, OCRC, IB, Campinas, SP - Brazil

^[4] Univ Sao Paulo, Dept Biochem, Sao Paulo - Brazil

^[5] Natl Lab Biosci, Campinas, SP - Brazil

^[6] Univ Mayor, Fac Ciencias, Ctr Genom & Bioinformat, Santiago - Chile

^[7] Univ Campinas UNICAMP, Lab Aging Biol LaBE, Dept Biochem & Tissue Biol, Program Genet & Mol Biol, Inst Biol, Campinas, SP - Brazil

^[8] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 - USA

^[9] Ecole Polytech Fed Lausanne, LISP, CH-1015 Lausanne - Switzerland

• Tipo de documento: Artigo Científico
• Fonte: Free Radical Biology and Medicine; v. 143, p. 203-208, NOV 1 2019.
• Citações Web of Science: 0

Resumo

The ability to respond to fluctuations of reactive oxygen species (ROS) within the cell is a central aspect of mammalian physiology. This dynamic process depends on the coordinated action of transcriptional factors to promote the expression of genes encoding for antioxidant enzymes. Here, we demonstrate that the transcriptional coregulators, PGC-1 alpha and NCoR1, are essential mediators of mitochondrial redox homeostasis in skeletal muscle cells. Our findings reveal an antagonistic role of these coregulators in modulating mitochondrial antioxidant induction through Sod2 transcriptional control. Importantly, the activation of this mechanism by either PGC-1 alpha overexpression or NCoR1 knockdown attenuates mitochondrial ROS levels and prevents cell death caused by lipid overload in skeletal muscle cells. The opposing actions of coactivators and corepressors, therefore, exert a commanding role over cellular antioxidant capacity. (AU)

• Processo FAPESP: 16/23008-5 - Identificação e caracterização funcional de proteína do complexo NCoR1 associada ao controle molecular do processo de biogênese mitocondrial
• Beneficiário: Leonardo dos Reis Silveira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/21628-9 - Plataforma biológica de triagem automatizada em larga escala (HTS) para a avaliação da homeostase mitocondrial em células aderidas
• Beneficiário: Tanes Imamura de Lima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/04377-2 - Estudo dos efeitos de Dicer sobre a função mitocondrial, o metabolismo e o envelhecimento em nematoides C. elegans
• Beneficiário: Silas Pinto da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado