The antioxidant requirement for plasma membrane repair in skeletal muscle
Free Radical Biology and Medicine Volume 84, July 2015, Pages 246–253 Mohamed Labazi
Highlights
• Vitamin E is required for skeletal muscle health.
• We hypothesized that the antioxidant vitamin E is required for plasma membrane repair in skeletal muscle.
• We found that repair is defective in the skeletal muscle of vitamin E-deprived rats.
• Depletion in cultured cells of glutathione 4 peroxidase, an enzyme with phospholipid hydroperoxidase activity, resulted in repair failure.
• We conclude that the antioxidant activity of vitamin E is required for muscle plasma membrane repair and is essential for skeletal muscle homeostasis.
Vitamin E (VE) deficiency results in pronounced muscle weakness and atrophy but the cell biological mechanism of the pathology is unknown. We previously showed that VE supplementation promotes membrane repair in cultured cells and that oxidants potently inhibit repair. Here we provide three independent lines of evidence that VE is required for skeletal muscle myocyte plasma membrane repair in vivo. We also show that when another lipid-directed antioxidant, glutathione peroxidase 4 (Gpx4), is genetically deleted in mouse embryonic fibroblasts, repair fails catastrophically, unless cells are supplemented with VE. We conclude that lipid-directed antioxidant activity provided by VE, and possibly also Gpx4, is an essential component of the membrane repair mechanism in skeletal muscle. This work explains why VE is essential to muscle health and identifies VE as a requisite component of the plasma membrane repair mechanism in vivo.