Mitophagy reporter mouse analysis reveals increased mitophagy activity in disuse‐induced muscle atrophy
Mitophagy reporter mouse analysis reveals increased mitophagy activity in disuse‐induced muscle atrophy
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DOI：
10.1002/jcp.30404
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发表时间：
2021-05
影响因子：
5.6
通讯作者：
S. Yamashita;Masanao Kyuuma;Keiichi Inoue;Y. Hata;R. Kawada;Masaki Yamabi;Yasuyuki Fujii;Junko Sakagami;Tomoyuki Fukuda;Kentaro Furukawa;Satoshi Tsukamoto;T. Kanki
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文献类型：
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作者：
S. Yamashita;Masanao Kyuuma;Keiichi Inoue;Y. Hata;R. Kawada;Masaki Yamabi;Yasuyuki Fujii;Junko Sakagami;Tomoyuki Fukuda;Kentaro Furukawa;Satoshi Tsukamoto;T. Kanki
肌肉废用会通过受损线粒体释放的活性氧（ROS）增加而导致肌肉萎缩。线粒体自噬（线粒体自噬降解）与 ROS 产生增加相关。然而，废用引起的肌肉萎缩期间线粒体自噬活性状态一直是争论的话题。在这里，我们开发了一种新的线粒体自噬报告小鼠系，以研究废用如何影响骨骼肌的线粒体自噬活性。然后使用在线粒体上表达串联 mCherry-EGFP 蛋白的小鼠来监测线粒体自噬活性的动态。报告小鼠在后肢固定 14 天后表现出线粒体自噬活性增强，萎缩的比目鱼肌中 ROS 产生增加。结果还显示多种线粒体自噬基因的表达增加，包括 Bnip3、Bnip3l 和 Park2。因此，我们的研究结果得出结论，废用增强了萎缩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引起的肌肉萎缩的潜在治疗靶点。
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.