Proton leak and hydrogen peroxide production in liver mitochondria from energy-restricted rats

Jon J Ramsey, Kevork Hagopian, Teresa M. Kenny, Edward K. Koomson, Lisa Bevilacqua, Richard Weindruch, Mary Ellen Harper

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Energy restriction (ER), without malnutrition, is the only environmental intervention that consistently increases maximum life span in laboratory rodents. One theory proposes that a reduction in energy expenditure and reactive oxygen species production is the mechanism responsible for this action of ER. To further test this theory, proton leak, H2O2 production, lipid peroxidation, and protein carbonyls were measured in mitochondria from FBNF1 rats fed either a control or 40% ER diet (onset at 6 mo of age). Liver mitochondria were isolated at 7 and 12 mo of age. Liver weight decreased 25 and 36% at 1 and 6 mo of ER, respectively (P < 0.05). ER resulted in an increase (P < 0.05) in percent total polyunsaturates, n-6 polyunsaturates, and total unsaturates (6 mo only) in mitochondrial lipids. These changes, however, were not associated with significant alterations in mitochondrial function. State 4 respiration and membrane potential were not different (P > 0.05) between groups at either assessment period. Similarly, proton leak kinetics were not different between control and ER animals. Top-down metabolic control analysis and its extension, elasticity analysis, were used at the 6-mo assessment and revealed no difference in control of the oxidative phosphorylation system between control and ER rats. H2O2 production with either succinate or pyruvate/malate substrates was also not different (P > 0.05) between groups at either time point. In conclusion, ER did not alter proton leak or H 2O2 production at this age or stage of restriction in liver.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number1 49-1
StatePublished - Jan 2004


  • Aging
  • Calorie restriction
  • Energy expenditure
  • Mitochondrial lipids
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry


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