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 Citations (Scopus)

Abstract

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
Volume1503
Issue number3
DOIs
StatePublished - Jan 19 2001

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Cytidine Monophosphate
Liver
Membrane Potentials
Muscle
Respiration
Nucleotides
Protons
Membranes
Muscles
Cytidine Triphosphate
Liver Mitochondrion
Adenosine Triphosphate
Mitochondria
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Proteins
Brown Adipose Tissue
Mitochondrial Proteins
Electron Transport
Chromatography
Carrier Proteins

Keywords

  • Proton leak
  • UCP2
  • UCP3
  • Uncoupling protein

ASJC Scopus subject areas

  • Biophysics

Cite this

Nucleotide effects on liver and muscle mitochondrial non-phosphorylating respiration and membrane potential. / Jekabsons, Mika B.; Horwitz, Barbara A.

In: Biochimica et Biophysica Acta - Bioenergetics, Vol. 1503, No. 3, 19.01.2001, p. 314-328.

Research output: Contribution to journalArticle

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