O'Leary Michael F N, Hood David A
School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, Ontario, Canada.
Autophagy. 2009 Feb;5(2):230-1. doi: 10.4161/auto.5.2.7391. Epub 2009 Feb 13.
Alterations in contractile activity influence the intracellular homeostasis of muscle, which results in adaptations in the performance and the phenotype of this tissue. Denervation is an effective disuse model that functions to change the intracellular environment of muscle leading to a rapid loss in mass, a decrease in mitochondrial content, and an elevation in both proapoptotic protein expression and myonuclear apoptosis. Recent investigations have shown that alternative degradation pathways such as autophagy are activated in conjunction with apoptosis during chronic muscle disuse. We have previously shown that seven days of muscle disuse increases the expression of Beclin 1. Furthermore, we have also detected a significant increase in the expression of LC3-II, a known component of autophagy. In addition to its upregulation, denervation appears to induce the translocation of LC3-II to mitochondrial membranes. Collectively, these increases in protein expression suggest that autophagy signaling is upregulated in response to denervation, and that these pathways may preferentially target mitochondria for degradation in skeletal muscle.
收缩活动的改变会影响肌肉的细胞内稳态，进而导致该组织的性能和表型发生适应性变化。去神经支配是一种有效的废用模型，其作用是改变肌肉的细胞内环境，导致肌肉质量迅速下降、线粒体含量减少以及促凋亡蛋白表达和肌核凋亡增加。最近的研究表明，在慢性肌肉废用期间，自噬等替代性降解途径会与凋亡一起被激活。我们之前已经表明，七天的肌肉废用会增加Beclin 1的表达。此外，我们还检测到自噬的已知成分LC3-II的表达显著增加。除了上调之外，去神经支配似乎还会诱导LC3-II转位至线粒体膜。总的来说，这些蛋白质表达的增加表明，自噬信号在去神经支配后被上调，并且这些途径可能优先靶向骨骼肌中的线粒体进行降解。
