Acute exercise rapidly activates hepatic mitophagic flux.

Exercise is critical for improving metabolic health and putatively maintains or enhances mitochondrial quality control in metabolic tissues. Although previous work has shown that exercise elicits hepatic mitochondrial biogenesis, it is unknown if acute exercise activates hepatic mitophagy, the selective degradation of damaged or low-functioning mitochondria. We tested if an acute bout of treadmill running increased hepatic mitophagic flux both right after and 2-h postexercise in 15- to 24-wk-old C57BL/6J female mice. Acute exercise did not significantly increase markers of autophagic flux, however, mitophagic flux was activated 2-h post-treadmill running as measured by accumulation of both LC3-II and p62 in isolated mitochondria in the presence of leupeptin, an inhibitor of autophagosome degradation. Furthermore, mitochondrial-associated ubiquitin, which recruits the autophagy receptor protein p62, was also significantly increased at 2 h. Further examination via Western blot and proteomics analysis revealed that acute exercise elicits a time-dependent, dynamic activation of mitophagy pathways. Moreover, the results suggest that exercise-induced hepatic mitophagy is likely mediated by both polyubiquitination and receptor-mediated signaling pathways. Overall, we provide evidence that acute exercise activates hepatic mitophagic flux while also revealing specific receptor-mediated proteins by which exercise maintains mitochondrial quality control in the liver. NEW & NOTEWORTHY This study provides evidence that acute exercise activates hepatic mitophagic flux and mitochondrial polyubiquitination while additionally revealing specific receptor-mediated proteins by which exercise maintains mitochondrial quality control in the liver.