Effect of aging, caloric restriction, and uncoupling protein 3 (UCP3) on mitochondrial proton leak in mice

Danny K. Asami, Roger B. McDonald, Kevork Hagopian, Barbara A Horwitz, David Warman, Aileen Hsiao, Craig H Warden, Jon J Ramsey

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Mitochondrial proton leak may modulate reactive oxygen species (ROS) production and play a role in aging. The purpose of this study was to determine proton leak across the life span in skeletal mitochondria from calorie-restricted and UCP2/3 overexpressing mice. Proton leak in isolated mitochondria and markers of oxidative stress in whole tissue were measured in female C57BL/6J mice fed ad-libitum (WT-Control) or a 30% calorie-restricted (WT-CR) diet, and in mice overexpressing UCP2 and UCP3 (Positive-TG), their non-overexpressing littermates (Negative-TG) and UCP3 knockout mice (UCP3KO). Proton leak in WT-CR mice was lower than that of control mice at 8 and 26 months of age. The Positive-TG mice had greater proton leak than the Negative-TG and UCP3KO mice at 8 months of age, but this difference disappeared by 19 and 26 months. Lipid peroxidation was generally lower in WT-CR vs. WT-Control mice and UCP3KO mice had greater concentrations of T-BARS (thiobarbituric acid reactive substances, a measure of lipid peroxidation) than did Positive-TG and Negative-TG. The results of this study indicate that sustained increases in muscle mitochondrial proton leak are not responsible for alterations in life span with calorie restriction or UCP3 overexpression in mice. However, UCP3 may contribute to the actions of CR through mechanisms distinct from increasing basal proton leak.

Original languageEnglish (US)
Pages (from-to)1069-1076
Number of pages8
JournalExperimental Gerontology
Issue number12
StatePublished - Dec 2008


  • Aging
  • Knockout mice
  • Lipid peroxidation
  • Mitochondrial oxygen consumption
  • Oxidative stress
  • Protein carbonyls

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Cell Biology
  • Endocrinology
  • Genetics
  • Molecular Biology


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