Mitochondrial‐targeted antioxidants attenuate immobilization‐induced skeletal muscle atrophy

Abstract

Prolonged periods of muscular inactivity (e.g., limb immobilization) result in skeletal muscle atrophy. Although is established that reactive oxygen species (ROS) play a role in inactivity‐induced skeletal muscle atrophy, the pathway(s) responsible for inactivity‐induced ROS production remain unclear. To investigate this important issue we tested the hypothesis that elevated mitochondrial ROS emission is essential for immobilization‐induced increases in oxidative stress and proteolysis in skeletal muscle. Cause and effect was determined by administering a novel mitochondrial‐targeted antioxidant (SS‐31) to prevent immobilization‐induced mitochondrial ROS emission in skeletal muscle fibers. Compared to ambulatory controls, 14‐days of immobilization resulted in decreased skeletal muscle mass along with increased mitochondrial ROS production, muscle oxidative damage, and protease activation. Importantly, treatment with SS‐31 attenuated the inactivity‐induced increase in mitochondrial ROS emission and prevented oxidative stress, protease activation, and fiber atrophy. These results support the hypothesis that redox disturbances are required for immobilization‐induced skeletal muscle atrophy and that mitochondria are a major source of ROS production in muscle fibers during prolonged periods of inactivity. Supported by NIH R01 HL087839 awarded to SKP