Fig. 2

Potential pathways of exercise-induced cardiac autophagy (EICA). Endurance exercise-induced AMPK activation initiates autophagy induction. Also, BCL2 phosphorylation (currently, responsible kinases for exercise-induced BLC2 phosphorylation have not been discovered) causes dissociation of BECLIN 1 from the BECLIN 1–BCL2 complexes and contributes to the initiation of phagophore formation and elongation. Upregulation of the rate-limiting autophagy enzyme ATG7 by endurance exercise increases autophagy flux, and studies have shown that FoxO3, a transcriptional activator which triggers apoptosis in the absence of survival factors, and hypoxia-inducible factor 1 (HIF1) upregulate LC3 and BNIP3, respectively, and thus enhance autophagy. Moreover, exercise-mediated reactive oxygen species (ROS) production has been suggested to induce autophagy elevation. Importantly, an activation of CALCINEURIN and inactivation (phosphorylation) of glycogen synthase kinase-3 (GSK3) cause the translocation of TFEB to the nucleus and gene expression associated with lysosomal biosynthesis, leading to autophagy enhancement