Bell Ryan A V, Al-Khalaf Mohammad, Megeney Lynn A
Regenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6 Canada ; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON Canada.
Regenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6 Canada ; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON Canada ; Department of Medicine, Division of Cardiology, University of Ottawa, Ottawa, ON Canada.
Skelet Muscle. 2016 Apr 6;6:16. doi: 10.1186/s13395-016-0086-6. eCollection 2016.
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.
由过度蛋白水解导致的肌肉萎缩是众多疾病状态的一个标志。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中的关键性质。在此，我们讨论主要的细胞蛋白水解机制——泛素/蛋白酶体系统、自噬/溶酶体系统以及半胱天冬酶介导的蛋白裂解——以及这些蛋白机制在建立和维持肌肉健康中的关键作用。我们研究有序降解如何改变：（1）成肌细胞分化过程中肌源性调节因子的时空表达；（2）肌管形成过程中的膜融合；（3）物理应激后肌节重塑和肌肉生长；以及（4）营养剥夺期间的能量稳态。最后，我们回顾一些肌病的起源和病因，以及这些毁灭性疾病如何由蛋白水解的先天性错误引发。
