The Role of PGC-1 alpha in Mediating Exercise-Induced TFEB Expression and Activity in Skeletal Muscle

A healthy mitochondrial pool in skeletal muscle is maintained by the coordinated processes of biogenesis and mitophagy. PGC-1alpha is a key transcriptional co-activator necessary for mitochondrial synthesis, whereas transcription factor EB (TFEB) regulates the degradation of dysfunctional organelles via activation of genes associated with autophagy. Despite TFEB's known role as a key regulator of autophagy and lysosomal genes, its response to exercise and the mechanisms behind its transcription and activation have yet to be elucidated. To identify TFEB's role and its dependence on PGC-1alpha, we subjected WT and PGC-1alpha KO mice to an acute bout of exercise and analyzed factors regulating TFEB transcription and nuclear translocation. We found a PGC-1alpha-dependent induction of TFEB transcription and activation with exercise, proving a strong correlation between the two processes involved in mitochondrial quality control.