School of Medicine and Health Sciences Poster Presentations
Injury Triggered Mitochondrial ROS Production Facilitates Repair of Injured Muscle Cells
Poster Number
10
Document Type
Poster
Publication Date
3-2016
Abstract
Skeletal muscle contraction produces the force needed for animal motility. This force generation requires energy produced by mitochondria, which facilitates actin-myosin movement required for muscle contraction. The resulting mechanical strain can damage the plasma membrane of individual skeletal myofibers. Unless rapidly repaired, these injuries can lead to death of the myofiber. We recently identified mitochondria in skeletal muscle as an integral requirement for the repair of plasma membrane damage; however, the mechanism by which mitochondria facilitate the repair of injured myofibers has not been resolved. Here, we used real-time imaging to monitor the spatial and temporal changes in muscle mitochondria and cytoskeleton after focal injury. Pharmacological inhibitors were used to investigate the role of mitochondrial activity and actin dynamics in the repair of injured plasma membrane. We find that calcium entering the muscle cell due to plasma membrane injury is taken up by mitochondria. Calcium increase causes increased oxidative phosphorylation and transient production of ROS by mitochondria. Blocking ROS, but not ATP production, compromises repair of injured cells. Mitochondrial calcium uptake is mediated by the mitochondrial calcium uniporter (MCU). Inhibition or genetic knockout of MCU compromises the ability of the cells to repair from focal injury. Calcium-triggered transient increase in mitochondrial ROS initiates signaling that promotes polymerization of F-actin at the site of injury. Blocking mitochondrial function, calcium uptake, and the ability of mitochondria to produce ROS all prevent plasma membrane repair by blocking actin polymerization. Similarly, a chronic increase in ROS also prevents actin polymerization and plasma membrane repair. These results identify a beneficial effect of mitochondrial ROS produced due to cell injury and demonstrate that mitochondria-mediated regulation of F-actin polymerization is the mechanism by which mitochondria facilitate repair of injured plasma membrane.
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Open Access
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Injury Triggered Mitochondrial ROS Production Facilitates Repair of Injured Muscle Cells
Skeletal muscle contraction produces the force needed for animal motility. This force generation requires energy produced by mitochondria, which facilitates actin-myosin movement required for muscle contraction. The resulting mechanical strain can damage the plasma membrane of individual skeletal myofibers. Unless rapidly repaired, these injuries can lead to death of the myofiber. We recently identified mitochondria in skeletal muscle as an integral requirement for the repair of plasma membrane damage; however, the mechanism by which mitochondria facilitate the repair of injured myofibers has not been resolved. Here, we used real-time imaging to monitor the spatial and temporal changes in muscle mitochondria and cytoskeleton after focal injury. Pharmacological inhibitors were used to investigate the role of mitochondrial activity and actin dynamics in the repair of injured plasma membrane. We find that calcium entering the muscle cell due to plasma membrane injury is taken up by mitochondria. Calcium increase causes increased oxidative phosphorylation and transient production of ROS by mitochondria. Blocking ROS, but not ATP production, compromises repair of injured cells. Mitochondrial calcium uptake is mediated by the mitochondrial calcium uniporter (MCU). Inhibition or genetic knockout of MCU compromises the ability of the cells to repair from focal injury. Calcium-triggered transient increase in mitochondrial ROS initiates signaling that promotes polymerization of F-actin at the site of injury. Blocking mitochondrial function, calcium uptake, and the ability of mitochondria to produce ROS all prevent plasma membrane repair by blocking actin polymerization. Similarly, a chronic increase in ROS also prevents actin polymerization and plasma membrane repair. These results identify a beneficial effect of mitochondrial ROS produced due to cell injury and demonstrate that mitochondria-mediated regulation of F-actin polymerization is the mechanism by which mitochondria facilitate repair of injured plasma membrane.
Comments
Presented at: GW Research Days 2016