It is known that muscle disuse reduces mitochondrial content and impairs mitochondrial function. Mitochondrial content is maintained, in part, by mitochondrial transcription factor A (TFAM), which control mitochondrial DNA transcription and replication. We thus sought to examine the expression of TFAM and the ways in which it may be regulated during muscle atrophy. We measured TFAM expression at a variety of levels, both transcriptionally and post-transcriptionally, and also examined any possible changes in TFAM intracellular localization. Tfam promoter activation in vivo was reduced at the early stages of denervation, while Tfam transcript half-life was increased following at the same time points. TFAM localization within subsarcolemmal mitochondria was reduced after chronic denervation, but did not precede the loss in mitochondrial content, and was associated with a suppression in mtDNA transcription. The relationship between TFAM expression and intracellular localization appears to be associated with, but not causal in the loss of mitochondrial content during muscle inactivity.
