The antioxidant requirement for plasma membrane repair in skeletal muscle

Free Radic Biol Med. 2015 Jul;84:246-253. doi: 10.1016/j.freeradbiomed.2015.03.016. Epub 2015 Apr 3.


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.

Keywords: Antioxidants; Free radicals; Membrane repair; Skeletal muscle; Vitamin E.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Glutathione Peroxidase / metabolism
  • Male
  • Mice
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / physiology
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology*
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Rats, Sprague-Dawley
  • Vitamin E / pharmacology*


  • Antioxidants
  • Vitamin E
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Glutathione Peroxidase