Article thumbnail

Carbon monoxide, skeletal muscle oxidative stress, and mitochondrial biogenesis in humans

By Michael A. Rhodes, Martha Sue Carraway, Claude A. Piantadosi, Crystal M. Reynolds, Anne D. Cherry, T. E. Wester, Michael J. Natoli, E. Wayne Massey, Richard E. Moon and Hagir B. Suliman


Given that the physiology of heme oxygenase-1 (HO-1) encompasses mitochondrial biogenesis, we tested the hypothesis that the HO-1 product, carbon monoxide (CO), activates mitochondrial biogenesis in skeletal muscle and enhances maximal oxygen uptake (V̇o2max) in humans. In 10 healthy subjects, we biopsied the vastus lateralis and performed V̇o2max tests followed by blinded randomization to air or CO breathing (1 h/day at 100 parts/million for 5 days), a contralateral muscle biopsy on day 5, and repeat V̇o2max testing on day 8. Six independent subjects underwent CO breathing and two muscle biopsies without exercise testing. Molecular studies were performed by real-time RT-PCR, Western blot analysis, and immunochemistry. After V̇o2max testing plus CO breathing, significant increases were found in mRNA levels for nuclear respiratory factor-1, peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor-A (Tfam), and DNA polymerase γ (Polγ) with no change in mitochondrial DNA (mtDNA) copy number or V̇o2max. Levels of myosin heavy chain I and nuclear-encoded HO-1, superoxide dismutase-2, citrate synthase, mitofusin-1 and -2, and mitochondrial-encoded cytochrome oxidase subunit-I (COX-I) and ATPase-6 proteins increased significantly. None of these responses were reproduced by V̇o2max testing alone, whereas CO alone increased Tfam and Polγ mRNA, and COX-I, ATPase-6, mitofusin-2, HO-1, and superoxide dismutase protein. These findings provide evidence linking the HO/CO response involved in mitochondrial biogenesis in rodents to skeletal muscle in humans through a set of responses involving regulation of the mtDNA transcriptosome and mitochondrial fusion proteins autonomously of changes in exercise capacity

Topics: Articles
Publisher: American Physiological Society
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.