Fig. 6

Summary of findings. Basally, females exhibit increased mitochondrial respiration and modestly reduced ROS emission, and this corresponds with heightened mitochondrial turnover supported by greater lysosomal content and higher basal mitophagy flux in comparison to males. Irrespective of sex, the loss of TFE3 results in a modest loss of mitochondrial content but does not impact lysosomal content. In response to 7 days of denervation, wild type males experience significant muscle atrophy and pronounced declines in mitochondrial content with a modest preservation in function. However, wildtype females appear to preserve mitochondrial content at the expense of function likely due to the reduction in denervation-induced mitophagy despite a robust lysosomal induction. The loss of TFE3 in males appears to shift the denervation-induced response towards that of a wildtype female in that mitochondrial content is modestly preserved at the expense of function. In the females, loss of TFE3 reduces the adaptive lysosomal response to denervation and the inhibitory effect on mitophagy is lost