Role of calcium signaling in the activation of mitochondrial nitric oxide synthase and citric acid cycle

Nathaniel Traaseth, Sarah Elfering, Joseph Solien, Virginia Haynes, Cecilia Giulivi

Research output: Contribution to journalReview articlepeer-review

Abstract

An apparent discrepancy arises about the role of calcium on the rates of oxygen consumption by mitochondria: mitochondrial calcium increases the rate of oxygen consumption because of the activation of calcium-activated dehydrogenases, and by activating mitochondrial nitric oxide synthase (mtNOS), decreases the rates of oxygen consumption because nitric oxide is a competitive inhibitor of cytochrome oxidase. To this end, the rates of oxygen consumption and nitric oxide production were followed in isolated rat liver mitochondria in the presence of either L-Arg (to sustain a mtNOS activity) or N G-monomethyl-L-Arg (NMMA, a competitive inhibitor of mtNOS) under State 3 conditions. In the presence of NMMA, the rates of State 3 oxygen consumption exhibited a K0.5 of 0.16 μM intramitochondrial free calcium, agreeing with those required for the activation of the Krebs cycle. By plotting the difference between the rates of oxygen consumption in State 3 with L-Arg and with NMMA at various calcium concentrations, a K0.5 of 1.2 μM intramitochondrial free calcium was obtained, similar to the K 0.5 (0.9 μM) of the dependence of the rate of nitric oxide production on calcium concentrations. The activation of dehydrogenases, followed by the activation of mtNOS, would lead to the modulation of the Krebs cycle activity by the modulation of nitric oxide on the respiratory rates. This would ensue in changes in the NADH/NAD and ATP/ADP ratios, which would influence the rate of the cycle and the oxygen diffusion.

Original languageEnglish (US)
Pages (from-to)64-71
Number of pages8
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1658
Issue number1-2
DOIs
StatePublished - Jul 23 2004

Keywords

  • Calcium
  • Cytochrome oxidase
  • Dehydrogenase
  • Krebs cycle
  • Mitochondria
  • Nitric oxide
  • Nitric oxide synthase
  • Oxygen

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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