Mitochondrial breakdown in skeletal muscle and the emerging role of the lysosomes

Skeletal muscle mitochondria are essential in providing the energy required for locomotion. In response to contractile activity, the production of mitochondria is upregulated to meet the energy demands placed upon muscle cells. In a coordinated fashion, exercise also promotes the breakdown of dysfunctional mitochondria via mitophagy. Mitophagy is characterized by the selection of poorly functioning organelles, engulfment in an autophagosome and transport to lysosomes for degradation. In addition to the activation of mitophagy, exercise also elevates lysosome biogenesis. This coordinated increase in mitophagy targeting and lysosomal biogenesis serves to enhance the capacity for autophagosomal degradation, thereby aiding in the maintenance of mitochondrial quality. Lysosome dysfunction, as observed in lysosomal storage disorders (LSDs), negatively impacts mitochondrial function likely through the suppression of mitophagy. Since exercise is capable of activating mitophagy and lysosome biogenesis, researchers have begun to investigate physical activity as an effective therapy for LSDs. This review summarizes the current understanding of how mitophagy and lysosomal biogenesis are regulated in exercising skeletal, with potential therapeutic implications. •Regulation of mitophagy is critical for the maintenance of mitochondrial health.•Endurance exercise is capable of activating mitophagy.•Lysosomes are required for autophagosomal breakdown.•Dysfunction of lysosomes produces muscle with mitochondrial abnormalities.•Exercise is therapeutic in lysosomal storage disorders affecting skeletal muscle.