Age-related increase in mitochondrial proton leak and decrease in ATP turnover reactions in mouse hepatocytes

Mary Ellen Harper, Shadi Monemdjou, Jon J Ramsey, Richard Weindruch

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Age-related changes in mitochondria, including decreased respiratory control ratios and altered mitochondrial inner membrane lipid composition, led us to study oxidative phosphorylation in hepatocytes from old (30 mo) and young (3 mo) male C57BL/J mice. Top-down metabolic control analysis and its extension, elasticity analysis, were used to identify changes in the control and regulation of the three blocks of reactions constituting the oxidative phosphorylation system: substrate oxidation, mitochondrial proton leak, and the ATP turnover reactions. Resting oxygen consumption of cells from old mice was 15% lower (P < 0.05) than in young cells. This is explained entirely by a decrease in oxygen consumption supporting ATP turnover reactions. At all values of mitochondrial membrane potential assessed, the proportion of total oxygen consumption used to balance the leak was greater in the old cells than in the young cells. Metabolic control coefficients indicate a shift in control over respiration and phosphorylation away from substrate oxidation toward increased control by leak and by ATP turnover reactions. Control of the actual number of ATP molecules synthesized by mitochondria for each oxygen atom consumed by the ATP turnover and leak reactions was greater in old than in young cells, showing that efficiency in older cells is more sensitive to changes in these two blocks of reactions than in young cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume275
Issue number2 38-2
StatePublished - Aug 1998
Externally publishedYes

Fingerprint

Protons
Hepatocytes
Adenosine Triphosphate
Oxygen Consumption
Oxygen
Mitochondria
Oxidative Phosphorylation
Oxidation
Phosphorylation
Mitochondrial Membrane Potential
Elasticity
Substrates
Membrane Lipids
Inbred C57BL Mouse
Respiration
Membranes
Atoms
Molecules
Chemical analysis

Keywords

  • Aging
  • Free radicals
  • Oxidative phosphorylation
  • Oxidative stress
  • Uncoupling

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry
  • Physiology (medical)

Cite this

Age-related increase in mitochondrial proton leak and decrease in ATP turnover reactions in mouse hepatocytes. / Harper, Mary Ellen; Monemdjou, Shadi; Ramsey, Jon J; Weindruch, Richard.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 275, No. 2 38-2, 08.1998.

Research output: Contribution to journalArticle

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