Increased mitochondrial proton leak in hepatocytes from old C57BL/J mice

M. E. Harper, S. Monemdjou, R. Weindruch, Jon J Ramsey

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Our aim was to compare the leakiness of the mitochondrial inner membrane (MIM) in hepatocytes from old (30 mo.) and young (3 mo.) C57Bl/J mice. Known age-related changes in mitochondria such as decreased state 3/state 4 ratio and changed MIM lipid composition led us to hypothesize that mitochondrial proton leak (leak) might be greater in cells from old compared to young mice. Our data support this. Resting oxygen consumption of cells (i.e. respiring on glucose, lactate, pyruvate and endogenous substrates) from old mice was 15% lower than in cells from young mice. The proportion of mitochondrial oxygen consumption used to support the leak was 101% greater in cells from old mice compared with young. There was no significant difference in extramitochondrial O2 consumption. The proportion of resting cellular oxygen consumption used to support ATP synthesis and turnover reactions was 56% and 67% in old and young mice respectively. We conducted a metabolic control analysis on data describing the kinetics of the three groupings of reactions comprising the oxidative phosphorylation system, i.e. substrate oxidation, ATP turnover and leak reactions. In cells from old mice there was a shift in control away from substrate oxidation reactions towards increased control by the leak and by ATP turnover reactions. Results provide further support for the oxidative stress theory of aging which includes free radical damage of the MIM.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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