Skeletal muscle heme oxygenase-1 activity regulates aerobic capacity

Rodrigo W. Alves de Souza, David Gallo, Ghee Rye Lee, Eri Katsuyama, Alexa Schaufler, Janick Weber, Eva Csizmadia, George C. Tsokos, Lauren G. Koch, Steven L. Britton, Ulrik Wisløff, Patricia C. Brum, Leo E. Otterbein

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Physical exercise has profound effects on quality of life and susceptibility to chronic disease; however, the regulation of skeletal muscle function at the molecular level after exercise remains unclear. We tested the hypothesis that the benefits of exercise on muscle function are linked partly to microtraumatic events that result in accumulation of circulating heme. Effective metabolism of heme is controlled by Heme Oxygenase-1 (HO-1, Hmox1), and we find that mouse skeletal muscle-specific HO-1 deletion (Tam-Cre-HSA-Hmox1fl/fl) shifts the proportion of muscle fibers from type IIA to type IIB concomitant with a disruption in mitochondrial content and function. In addition to a significant impairment in running performance and response to exercise training, Tam-Cre-HSA-Hmox1fl/fl mice show remarkable muscle atrophy compared to Hmox1fl/fl controls. Collectively, these data define a role for heme and HO-1 as central regulators in the physiologic response of skeletal muscle to exercise.

Original languageEnglish
Article number109018
JournalCell Reports
Issue number3
Publication statusPublished - Apr 20 2021
Externally publishedYes


  • DAMP
  • exercise training
  • heme
  • heme oxygenase-1
  • hemopexin
  • mitochondrial dysfunction
  • muscle atrophy
  • muscle microtrauma
  • satellite cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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