The beneficial role of proteolysis in skeletal muscle growth and stress adaptation.
The beneficial role of proteolysis in skeletal muscle growth and stress adaptation.
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DOI：
10.1186/s13395-016-0086-6
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发表时间：
2016
期刊：
影响因子：
4.9
通讯作者：
Megeney LA
中科院分区：
文献类型：
--
作者：
Bell RA;Al-Khalaf M;Megeney LA
过度蛋白水解引起的肌肉萎缩是许多疾病的标志。因此，骨骼肌蛋白分解的负面后果常常掩盖了蛋白水解系统在维持正常细胞功能方面的关键性质。在这里，我们讨论主要的细胞蛋白水解机制——泛素/蛋白体系统、自噬/溶酶体系统和半胱天冬酶介导的蛋白质裂解——以及这些蛋白质机制在建立和维持肌肉健康中的关键作用。我们研究了有序降解如何改变（1）成肌细胞分化过程中生肌调节因子的时空表达，（2）肌管形成过程中的膜融合，（3）物理应激后的肌节重塑和肌肉生长，以及（4）营养剥夺过程中的能量稳态。最后，我们回顾了许多肌病的起源和病因，以及这些破坏性病症是如何由先天性蛋白水解错误引起的。
Muscle atrophy derived from excessive proteolysis is a hallmark of numerous disease conditions. Accordingly, the negative consequences of skeletal muscle protein breakdown often overshadow the critical nature of proteolytic systems in maintaining normal cellular function. Here, we discuss the major cellular proteolysis machinery—the ubiquitin/proteosome system, the autophagy/lysosomal system, and caspase-mediated protein cleavage—and the critical role of these protein machines in establishing and preserving muscle health. We examine how ordered degradation modifies (1) the spatiotemporal expression of myogenic regulatory factors during myoblast differentiation, (2) membrane fusion during myotube formation, (3) sarcomere remodeling and muscle growth following physical stress, and (4) energy homeostasis during nutrient deprivation. Finally, we review the origin and etiology of a number of myopathies and how these devastating conditions arise from inborn errors in proteolysis.