Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Discovery Research Laboratories, Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
J Cell Physiol. 2021 Nov;236(11):7612-7624. doi: 10.1002/jcp.30404. Epub 2021 May 2.
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.
肌肉废用会导致受损线粒体释放的活性氧（ROS）增加，从而引起萎缩。自噬体吞噬线粒体的自噬降解与 ROS 产生增加有关。然而，废用性肌肉萎缩过程中自噬体的活性状态一直存在争议。在这里，我们开发了一种新的自噬体报告小鼠系，以研究废用如何影响骨骼肌中的自噬体活性。然后使用在线粒体上表达串联 mCherry-EGFP 蛋白的小鼠来监测自噬体活性的动力学。报告小鼠在 14 天的后肢固定后，萎缩的比目鱼肌中的自噬体活性增强，ROS 产生增加。结果还显示，多种自噬体基因的表达增加，包括 Bnip3、Bnip3l 和 Park2。因此，我们的研究结果得出结论，废用会增强萎缩骨骼肌中的自噬体活性和 ROS 产生，并表明自噬体是废用性肌肉萎缩的潜在治疗靶点。
