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

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: Free Radical Biology and Medicine; v. 143, p. 203-208, NOV 1 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 16/23008-5 - Identification and functional characterization of protein bound to NCoR1 complex and associated with molecular control of mitochondrial biogenesis process
• Grantee: Leonardo dos Reis Silveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/21628-9 - High throughput screening (HTS) biological platform for mitochondrial homeostasis evaluation in adherent cells
• Grantee: Tanes Imamura de Lima
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/04377-2 - Study of Dicer effects on mitochondrial function, metabolism and aging in C. elegans nematodes
• Grantee: Silas Pinto da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate