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

Opposing action of NCoR1 and PGC-1α in mitochondrial redox homeostasis. Free Radic Biol Med. 2019 Aug 10;: Authors: Lima TI, Guimarães DSPSF, Oliveira AG, Araujo H, Sponton CHG, Pinto NS, Saito A, Figueira ACM, Palameta S, Bajgelman MC, Calixto A, Pinto S, Mori MA, Orofino J, Perissi V, Mottis A, Auwerx J, Silveira LR 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-1α 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-1α 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. PMID: 31408725 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research