Nucleotide effects on liver and muscle mitochondrial non-phosphorylating respiration and membrane potential

Mika B. Jekabsons, Barbara A Horwitz

Research output: Contribution to journalArticle

2 Scopus citations


Uncoupling protein-1 homologs are hypothesized to mediate mitochondrial proton leak. To test this hypothesis, we determined the effects of ATP and other nucleotides on liver and skeletal muscle mitochondrial non-phosphorylating respiration (VO2), membrane potential, FCCP-stimulated respiratory control ratios, and swelling. Neither ATP nor CTP affected liver or muscle proton leak, but both inhibited the respiratory chain. Unexpectedly, CMP stimulated liver proton leak (EC50~4.4±0.5 mM). Using CMP chromatography, we identified two proteins (M(r)=31.2 and 32.6 kDa) from liver mitochondria that are similar in size to members of the mitochondrial carrier protein family. We conclude (a) liver and muscle mitochondrial proton leak is insensitive to ATP and CTP, and (b) CMP activates a leak in liver mitochondria. The CMP-inducible leak may be mediated by a 30-32 kDa protein. Based on the high concentrations required, CMP is unlikely to be a physiologically important leak regulator. Nonetheless, our results show that tissues other than brown fat have inducible leaks that may be protein-mediated. Copyright (C) 2001 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)314-328
Number of pages15
JournalBiochimica et Biophysica Acta - Bioenergetics
Issue number3
StatePublished - Jan 19 2001



  • Proton leak
  • UCP2
  • UCP3
  • Uncoupling protein

ASJC Scopus subject areas

  • Biophysics

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