Search and characterization of novel transcriptional regulators of mitochondrial biogenesis associated genes

Abstract

The mitochondria have fundamental roles in a series of cellular processes, in such a way that their activity level and number in each cell must follow the fuel requirement changes and dysfunctions in the regulation of this processes may lead to conditions like Obesity and Diabetes. Classically, o major regulator of mitochondrial biogenesis is the PGC1-a protein, which by interacting with nuclear receptors like PPAR, ESRR, and chromatin modifiers, controls the transcription of genes related to the mitochondrial biogenesis and mitochondrial oxidative capacity. However, recent studies have shown the PGC1-a protein and its homolog, PGC1-b, are not necessary to in vivo mitochondrial biogenesis, thereby indicating the existence of crucial PGC1 independent mechanisms. Therefore, we are proposing the search for novel regulators of mitochondrial biogenesis using C2C12 cells in differentiation and the in vitro and in vivo molecular characterizations of this regulators. Our study will contribute to the elucidation of molecular mechanisms of mitochondrial biogenesis and to a better understanding of Diabetes and Obesity etiology. (AU)