Kim, Y and Hood DA. Regulation of the autophagy system during chronic contractile activity-induced muscle adaptations. Physiol Rep. 2017, 5 (14), e13307.
Significance of the research: "As skeletal muscle comprises a majority of body mass, the mitochondria within this tissue are of paramount importance in maintaining the metabolic status of an individual. Regular exercise training can increase metabolic health by expanding the mitochondrial pool within muscle and “clearing out” unhealthy organelles, thus establishing an optimal network capable of matching the metabolic needs of the cell. These balancing processes are referred to as mitochondrial synthesis (biogenesis) and degradation (mitophagy), respectively, and our lab has studied these processes in depth within skeletal muscle. Mitochondrial biogenesis is well known to be induced with exercise through the upregulation of the transcriptional regulators like, PGC-1a. More recent work has demonstrated that along with mitochondrial biogenesis, skeletal muscle cells undergo considerable mitophagy which is equally important in regulating the content of mitochondria muscle. Mitophagy involves the degradation of cellular cargo like mitochondria by the lysosome. Similar to the role of PGC-1a in regulating mitochondrial biogenesis, the transcriptional protein TFEB has been implicated as the regulator of lysosomal biogenesis and mitophagy. In this paper, we shed further light on the balance of these process and establish a time-course of adaptation throughout a training study. To do this we chronically stimulated the hindlimbs of rats to contract for 6 hours per day for 1, 3 or 7 days. This chronic contractile activity model is capable of producing similar increases in mitochondrial content within 7 days as a 6-week running study. Here we found that mitophagy was initiated coincident with mitochondrial biogenesis. We also found that lysosomal adaptations appear to precede the adaptations related to mitochondrial biogenesis and mitophagy. Therefore, these results establish for the first time the coordination of these processes and suggest that exercise promotes a change in lysosomal biogenesis that is necessary for increasing the capacity of muscle cells to accommodate elevations in mitophagy to keep the mitochondrial pool healthy."