Identification and functional characterization of protein bound to NCoR1 complex and associated with molecular control of mitochondrial biogenesis process.

Abstract

Skeletal muscle uses a well regulated transcriptional programs to adapt to environmental inputs through storage or consumption of energy. PPAR² plays a critical role in this pro-cess being regulated by its interaction with positive and negative co-regulators. Under NCoR1 overexpression, a well known PPAR inhibitor, we observed a marked repression of mitochondrial biogenesis in C2C12 cells during the differentiation process. This effect was demonstrated to reduce mitochondrial respiration, mitochondrial content, oxidative proteins, tricarboxylic acid cycle intermediates and to increase glycolysis activity. In addi-tion, this phenotype was consistent with reduced transcription of a wide spectrum of genes associated with mitochondrial metabolism as determined by RNAseq technique. However, it is unclear who are the players which interact with NCoR1 during its repres-sion activity over PPAR². More interesting, is the question if NCor1 could interacting with other molecular target regulating mitochondrial biogenesis by a mechanism inde-pendent of PPAR. Therefore, considering the NCoR1 effect over mitochondrial metabo-lism we raised the hypothesis that NCoR1 could works as very promising tool on discov-ery new molecular target(s) to control of mitochondrial biogenesis process in skeletal muscle cells.