Autophagy/mitophagy, a cellular catabolic process necessary for sustaining normal cellular function, has emerged as a potential therapeutic strategy against numerous obstinate diseases. In this regard, endurance exercise (EXE)-induced autophagy/mitophagy (EIAM) has been considered as a potential health-enriching factor in various tissues including the brain; however, underlying mechanisms of EIAM in the brain has not been fully defined yet. This study investigated the molecular signaling nexus of EIAM pathways in the cortex of the brain. C57BL/6 young male mice were randomly assigned to a control group (CON, n = 12) and an endurance exercise group (EXE, n = 12). Our data demonstrated that exercise-induced autophagy coincided with an enhanced anabolic state (p-AKT, p-mTOR, and p-p70S6K); furthermore, mitophagy concurred with enhanced mitochondrial turnover: increases in both fission (DRP1, BNIP3, and PINK1) and fusion (OPA1 and MFN2) proteins. In addition, neither oxidative stress nor sirtuins (SIRT) 1 and 3 were associated with EIAM; instead, the activation of AMPK as well as a JNK-BCL2 axis was linked to EIAM promotion. Collectively, our results demonstrated that EXE-induced anabolic enrichment did not hinder autophagy/mitophagy and that the concurrent augmentation of mitochondrial fusion and fusion process contributed to sustaining mitophagy in the cortex of the brain. Our findings suggest that the EXE-induced concomitant potentiation of the catabolic and anabolic state is a unique molecular mechanism that simultaneously contributes to recycling and rebuilding the cellular structure, leading to upholding healthy cellular environment. Thus, the current study provides a novel autophagy/mitophagy mechanism, from which groundbreaking pharmacological strategies of autophagy can be developed.
Keywords: AMPK; Autophagy; Cortex; Endurance exercise; Mitophagy; mTOR.