More than just a garbage can: emerging roles of the lysosome as an anabolic organelle in skeletal muscle

Sidney Abou Sawan, Michael Mazzulla, Daniel R Moore, Nathan Hodson
American Journal of Physiology. Cell Physiology 2020 July 29
Skeletal muscle is a highly plastic tissue capable of remodeling in response to a range of physiological stimuli including nutrients and exercise. Historically, the lysosome has been considered an essentially catabolic organelle contributing to autophagy, phagocytosis, and exo/endocytosis in skeletal muscle. However, recent evidence has emerged of several anabolic roles for the lysosome including the requirement for autophagy in skeletal muscle mass maintenance, the discovery of the lysosome as an intracellular signaling hub for mTORC1 activation, and the importance of TFEB/lysosomal biogenesis-related signaling in the regulation of mTORC1-mediated protein synthesis. We therefore propose that the lysosome is an understudied organelle with the potential to underpin the skeletal muscle adaptive response to anabolic stimuli. Within this review we describe the molecular regulation of lysosome biogenesis and detail the emerging anabolic roles of the lysosome in skeletal muscle with particular emphasis on how these roles may mediate adaptations to chronic resistance exercise. Furthermore, given the well-established role of amino acids to support muscle protein remodeling, we describe how dietary proteins 'labeled' with stable isotopes could provide a complimentary research tool to better understand how lysosomal biogenesis, autophagy regulation, and/or mTORC1-lysosomal repositioning can mediate the intracellular usage of dietary amino acids in response anabolic stimuli. Finally, we provide avenues for future research with the aim of elucidating how the regulation of this important organelle could mediate skeletal muscle anabolism.

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