Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production

Florian L. Muller, Wook Song, Youngmok C. Jang, Yuhong Liu, Marian Sabia, Arlan Richardson, Holly Van Remmen

Research output: Contribution to journalArticlepeer-review

199 Scopus citations


Reactive oxygen species (ROS), especially mitochondrial ROS, are postulated to play a significant role in muscle atrophy. We report a dramatic increase in mitochondrial ROS generation in three conditions associated with muscle atrophy: in aging, in mice lacking CuZn-SOD (Sod1-/-), and in the neurodegenerative disease, amyotrophic lateral sclerosis (ALS). ROS generation in muscle mitochondria is nearly threefold higher in 28- to 32-mo-old than in 10-mo-old mice and is associated with a 30% loss in gastrocnemius mass. In Sod1-/- mice, muscle mitochondrial ROS production is increased >100% in 20-mo compared with 5-mo-old mice along with a >50% loss in muscle mass. ALS G93A mutant mice show a 75% loss of muscle mass during disease progression and up to 12-fold higher muscle mitochondrial ROS generation. In a second ALS mutant model, H46RH48Q mice, ROS production is approximately fourfold higher than in control mice and is associated with a less dramatic loss (30%) in muscle mass. Thus ROS production is strongly correlated with the extent of muscle atrophy in these models. Because each of the models of muscle atrophy studied are associated to some degree with a loss of innervation, we were interested in determining whether denervation plays a role in ROS generation in muscle mitochondria isolated from hindlimb muscle following surgical sciatic nerve transection. Seven days postdenervation, muscle mitochondrial ROS production increased nearly 30-fold. We conclude that enhanced generation of mitochondrial ROS may be a common factor in the mechanism underlying denervation-induced atrophy.

Original languageEnglish (US)
Pages (from-to)R1159-R1168
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3
StatePublished - Sep 2007


  • Amyotrophic lateral sclerosis
  • Copper, zinc superoxide dismutase
  • Mitochondria
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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