Acute Exercise‐Induced Mitophagy is Mediated in Part by PGC‐1α

Abstract

Chronic exercise results in systemic metabolic benefits in the major metabolic centers of the body. Skeletal muscle is a pillar of whole body metabolism and this tissue undergoes metabolic remodelling with repeated bouts of contractile activity. This is accomplished by increased mitochondrial turnover with a concurrent increase in both organelle biogenesis and removal. While biogenesis is largely orchestrated by the transcriptional co-activator PGC-1α, the regulation of mitochondrial degradation (i.e mitophagy) is less well established. Coincidentally, both mitochondrial biogenesis and autophagy are activated by an acute bout of exercise. However, the induction of mitophagy following exercise, and the interplay between autophagy and PGC-1α following acute exercise, have not been thoroughly examined. To address this, we subjected wild type (WT) and PGC-1α knockout animals (KO) to an acute bout of exhaustive exercise. Lack of PGC-1α resulted in a 40% drop in mitochondrial content and a 25% decline in running performance. KO mice also depicted a greater increase and a slower recovery of blood lactate following exercise, indicating metabolic distress. Indeed, exercise-induced activation of AMPK and p38 was greater in KO as compared to WT animals. Exercise also induced a 2-3-fold increase in gene transcripts of various mitochondrial (e.g COXIV, Tfam) and autophagy-related genes (e.g. p62, LC3) in WT animals only. Moreover, both autophagy and mitophagy flux were induced by exercise, but this increase was attenuated in KO animals. These results suggest that an acute bout of exercise is sufficient to induce mitochondrial turnover through increased biogenesis and degradation. Moreover, these two processes appear to be, at least in part, regulated by PGC-1α.