Figure 2.

Overview of molecular mediators of exercise-induced autophagy and the autophagy-dependent beneficial effects of exercise. Exercise-induced activation of autophagy in skeletal muscle has been shown to be influenced by transcriptional regulation of autophagy-related genes (ATGs) mediated by forkhead box O (FOXO) family of transcription factors, transcription factor EB (TFEB), p53, and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) to increase the autophagic capacity. The oxidative phenotype of skeletal muscle is linked to autophagy capacity/flux and is positively regulated by the exercise responsive 5′ AMP-activated protein kinase (AMPK) and PGC-1α. AMPK and mammalian target of rapamycin (mTOR) act as an activator and suppressor of exercise-induced autophagy, respectively. Exercise-induced generation of reactive oxygen species (ROS) seems to serve as a signal for autophagy activation. Autophagy-dependent beneficial effects of exercise include degradation of oxidatively damaged proteins and organelles, improved mitochondrial oxidative capacity, improved glucose regulation, protein synthesis, preservation of muscle strength and mass, and improved endurance exercise performance.