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More than just a garbage can: emerging roles of the lysosome as an anabolic organelle in skeletal muscle.
American Journal of Physiology-Cell Physiology ( IF 5.0 ) Pub Date : 2020-07-29 , DOI: 10.1152/ajpcell.00241.2020
Sidney Abou Sawan 1 , Michael Mazzulla 1 , Daniel R Moore 1 , Nathan Hodson 1
Affiliation  

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.

中文翻译:

不仅仅是一个垃圾桶:溶酶体在骨骼肌中作为合成代谢细胞器的新兴作用。

骨骼肌是一种高度可塑性的组织,能够响应包括营养和运动在内的一系列生理刺激而重塑。从历史上看,溶酶体被认为是一种主要的分解代谢细胞器,有助于骨骼肌中的自噬、吞噬作用和外/内吞作用。然而,最近的证据表明溶酶体具有多种合成代谢作用,包括骨骼肌质量维持中自噬的需要,发现溶酶体作为 mTORC1 激活的细胞内信号中心,以及 TFEB/溶酶体生物发生相关信号在mTORC1 介导的蛋白质合成的调节。因此,我们提出溶酶体是一种未被充分研究的细胞器,具有支持骨骼肌对合成代谢刺激的适应性反应的潜力。在这篇综述中,我们描述了溶酶体生物发生的分子调控,并详细介绍了溶酶体在骨骼肌中新出现的合成代谢作用,特别强调了这些作用如何调节对慢性阻力运动的适应。此外,鉴于氨基酸在支持肌肉蛋白质重塑方面的公认作用,我们描述了用稳定同位素“标记”的膳食蛋白质如何提供补充研究工具,以更好地了解溶酶体生物发生、自噬调节和/或 mTORC1-溶酶体重新定位可以介导膳食氨基酸的细胞内使用以响应合成代谢刺激。最后,我们为未来的研究提供了途径,目的是阐明这一重要细胞器的调节如何介导骨骼肌合成代谢。
更新日期:2020-08-20
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