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Abstract：
Muscle disuse induces atrophy through increased reactive oxygen species (ROS) released from damaged mitochondria. Mitophagy, the autophagic degradation of mitochondria, is associated with increased ROS production. However, the mitophagy activity status during disuse-induced muscle atrophy has been a subject of debate. Here, we developed a new mitophagy reporter mouse line to examine how disuse affected mitophagy activity in skeletal muscles. Mice expressing tandem mCherry-EGFP proteins on mitochondria were then used to monitor the dynamics of mitophagy activity. The reporter mice demonstrated enhanced mitophagy activity and increased ROS production in atrophic soleus muscles following a 14-day hindlimb immobilization. Results also showed an increased expression of multiple mitophagy genes, including Bnip3, Bnip3l, and Park2. Our findings thus conclude that disuse enhances mitophagy activity and ROS production in atrophic skeletal muscles and suggests that mitophagy is a potential therapeutic target for disuse-induced muscle atrophy.
摘要：
肌肉废用通过从受损线粒体释放的活性氧（ROS）增加而引起萎缩。线粒体自噬,线粒体的自噬降解，与ROS产量增加有关。然而,废用性肌肉萎缩过程中的线粒体自噬活性状态一直是争论的话题.这里,我们开发了一种新的mitophagy报道小鼠线，以检查废用如何影响骨骼肌中的mitophagy活动。然后使用在线粒体上表达串联mCherry-EGFP蛋白的小鼠来监测线粒体自噬活性的动力学。报告小鼠在14天后肢固定后，在萎缩的比目鱼肌中表现出增强的线粒体自噬活性和增加的ROS产生。结果还显示多个线粒体自噬基因的表达增加，包括Bnip3，Bnip3l，Park2因此，我们的发现得出结论，废用可增强萎缩性骨骼肌中的线粒体自噬活性和ROS产生，并表明线粒体自噬是废用诱导的肌肉萎缩的潜在治疗靶标。
