Abstract
Skeletal muscles are proficient at healing from a variety of injuries. Healing occurs in two phases, early and late phase. Early phase involves healing the injured sarcolemma and restricting the spread of damage to the injured myofiber. Late phase of healing occurs a few days postinjury and involves interaction of injured myofibers with regenerative and inflammatory cells. Of the two phases, cellular and molecular processes involved in the early phase of healing are poorly understood. We have implemented an improved sarcolemmal proteomics approach together with in vivo labeling of proteins with modified amino acids in mice to study acute changes in the sarcolemmal proteome in early phase of myofiber injury. We find that a notable early phase response to muscle injury is an increased association of mitochondria with the injured sarcolemma. Real-time imaging of live myofibers during injury demonstrated that the increased association of mitochondria with the injured sarcolemma involves translocation of mitochondria to the site of injury, a response that is lacking in cultured myoblasts. Inhibiting mitochondrial function at the time of injury inhibited healing of the injured myofibers. This identifies a novel role of mitochondria in the early phase of healing injured myofibers.
Highlights
Cellular processes involved in healing injured skeletal muscle fibers are poorly understood
We find that a notable early phase response to muscle injury is an increased association of mitochondria with the injured sarcolemma
Isolation of Sarcolemmal Proteome Using the Membrane Solubilization Approach—Use of biotin tagging of cell surface proteins together with streptavidin beads has been used to pull down cell surface proteins from cells and tissue [25, 26]
Summary
Cellular processes involved in healing injured skeletal muscle fibers are poorly understood. We find that a notable early phase response to muscle injury is an increased association of mitochondria with the injured sarcolemma. Monitoring dynamic changes in the sarcolemmal proteome would improve our understanding of how these two phases are regulated and help to better understand various neuromuscular disorders associated with defects in myofiber degeneration and regeneration [6, 9] Such changes have been studied during the late phase of healing; little is known about such changes during the early phase of myofiber healing [2, 3, 7, 8]. Another approach has exploited the electrostatic interaction between cationic colloidal silica and anionic membrane lipids on the cell surface to increase the stability and density of the plasma membrane and, subsequently, to separate it using centrifugation [29] These approaches for isolating sarcolemmal proteome from muscles rely on the use of a large amount of tissue
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