Regulation of Tfam expression at the onset of muscle disuse

Abstract

Chronic muscle disuse, such as that produced by long‐term denervation, results in a loss of muscle mass in addition to reductions in mitochondrial content and function. However, acute alterations in the expression of factors regulating mitochondrial content, namely mitochondrial transcription factor A (Tfam), have yet to be elucidated following denervation. Thus, to investigate changes in Tfam expression, we employed the in vivo transfection of a Tfam promoter‐luciferase reporter construct into rat tibialis anterior muscle denervated for 0, 8, 16, 24, 72 or 120 hours. Tfam transcription was reduced by 40–70% between 8 and 24 hours of denervation. This was reflected in a 30% reduction in Tfam mRNA content by 24 hours of denervation, which occurred without any notable changes in Tfam mRNA stability. These changes in Tfam transcription and mRNA preceded alterations in mitochondrial content and muscle mass, first noted by 72 and 120 hours, respectively. Our data suggest that denervation results in early changes in gene expression regulating mitochondrial content, which precede subsequent decrements in muscle mass during disuse conditions. Further investigation of the upstream signals governing Tfam expression in muscle is warranted. Supported by NSERC.