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Updated: Nov 7, 2025
In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
Published on: November 22, 2017
Mitophagy reporter mouse analysis reveals increased mitophagy activity in disuse-induced muscle atrophy
Shun-Ichi Yamashita1, Masanao Kyuuma2, Keiichi Inoue1
1Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
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.
Insights
Muscle disuse causes atrophy by increasing reactive oxygen species (ROS). This study found that mitophagy activity and ROS production are enhanced in atrophied skeletal muscles, suggesting mitophagy as a therapeutic target.
Area of Science:
- Muscle physiology
- Cellular biology
- Mitochondrial dynamics
Background:
- Muscle disuse leads to atrophy, partly due to increased reactive oxygen species (ROS) from damaged mitochondria.
- Mitophagy, the selective removal of damaged mitochondria, is linked to ROS production, but its role in disuse atrophy is debated.
Purpose of the Study:
- To investigate the activity status of mitophagy in skeletal muscles during disuse-induced atrophy.
- To develop and utilize a novel mitophagy reporter mouse model for dynamic monitoring.
Main Methods:
- Development of a mitophagy reporter mouse line expressing tandem mCherry-EGFP on mitochondria.
- Induction of hindlimb immobilization for 14 days to simulate muscle disuse.
- Analysis of mitophagy activity, ROS production, and mitophagy gene expression in soleus muscles.
Main Results:
- Immobilization significantly enhanced mitophagy activity in atrophic soleus muscles.
- Increased ROS production was observed concurrently with enhanced mitophagy.
- Expression of key mitophagy genes (Bnip3, Bnip3l, Park2) was upregulated.
Conclusions:
- Disuse-induced muscle atrophy is associated with heightened mitophagy activity and ROS production.
- Mitophagy plays a significant role in the pathophysiology of disuse atrophy.
- Targeting mitophagy presents a potential therapeutic strategy for mitigating muscle atrophy.
