自噬-溶酶体途径与骨骼肌和膈肌萎缩的研究进展

Research progress of involvement of autophagy-lysosomal system in skeletal muscle and diaphragm atrophy

骨骼肌是人体重要的运动器官和能量代谢靶器官。呼吸肌是特殊的骨骼肌,因为它们在生命过程中持续运动。膈肌是最主要的吸气肌,相较外周骨骼肌,其血供更为丰富,抗疲劳能力和氧化代谢能力更强。多种疾病状态下均可出现骨骼肌和膈肌萎缩及功能异常。肌萎缩的主要机制为蛋白分解增加而蛋白合成下降,而病理状态下肌萎缩主要由肌肉蛋白分解增加造成。自噬-溶酶体(autophagy-lysosome,AL)途径在维持骨骼肌质量动态平衡中起重要作用,其主要功能是将细胞质中多余或损伤的蛋白和细胞器运输至溶酶体进行降解。适当活性的AL途径能通过清除细胞代谢产物来保持内稳态,在维持骨骼肌质量中起保护作用;而过度激活的AL途径能使蛋白分解状态加重,导致肌萎缩。本文就AL途径在骨骼肌和膈肌萎缩中所起的作用及其机制作一综述。

Skeletal muscles are the body＇ s agent of motion and important sites for the control of metabolism. The respiratory muscles are unique among skeletal muscles,since they must work without sustained rest throughout life. The diaphragm is the principal inspiratory pump muscle,it is more resistant to developing fatigue than limb muscles. The blood flow and the oxidative capacity of the diaphragm exceed those of limb muscles. Muscle atrophy and contractile dysfunction can be found in a variety of diseases. The reductions in muscle mass is tilted toward reduced protein synthesis and enhanced protein degradation. During pathologic conditions,enhanced protein breakdown is the main reason resulting in myofiber atrophy. Recent studies have underlined a critical role for the autophagy-lysosome（ AL） system in regulating muscle mass.The main function of AL system involves the delivery of cytoplasmic cargo sequestered inside doublemembrane vesicles to the lysosome which can eliminate the cell of superfluous or damaged organelles and proteins. Basal autophagy is necessary to muscle homeostasis,since it is responsible for the removal of intracellular metabolites. But excessive activation of autophagy can aggravate catabolism and contribute to muscle loss. This review focuses on the AL system and discusses its beneficial or detrimental role in skeletal and diaphragm atrophy.