The adoption of a regular exercise program has immense benefits for whole body health, and for improving the quality of skeletal muscle. This is important as muscle is involved in metabolism, locomotion, and force production, making it a large contributor to the quality of life. The coordinated behavior of several intracellular organelles is responsible for the maintenance of skeletal muscle health, and these organelles are adaptable in response to both acute and chronic exercise. While the adaptations of mitochondria to exercise are well-established, potential alterations in muscle lysosomes are less appreciated. Lysosomes degrade and recycle debris during the terminal step of various forms of autophagy, such as mitophagy, the pathway involved in the removal of dysfunctional mitochondria. This lysosomal activity is important for the maintenance of cellular protein and organelle homeostasis. Recent work has shown that lysosome biogenesis begins with every acute bout of exercise, driven by the nuclear translocation of regulatory transcription factors such as TFEB and TFE3, which mediate the transcription of autophagy and lysosomal genes. These transcription factors also play a role in other pathways such as chaperone-mediated autophagy (CMA) and the regeneration of existing lysosomes through the autophagic-lysosome reformation (ALR) pathway. When performed repeatedly, acute bouts of exercise elicit a longer-term adaptive response, leading to the formation of active lysosomes, which increase lysosomal degradative capacity in skeletal muscle. This review addresses the current knowledge surrounding the effects of acute and chronic exercise on lysosomal adaptations in skeletal muscle, highlighting a novel pathway of muscle plasticity.
