Ca2+ activation of heart mitochondrial oxidative phosphorylation: Role of the F0/F1-ATPase

Paul Territo, Vamsi K. Mootha, Stephanie A. French, Robert S. Balaban

Research output: Contribution to journalArticle

263 Citations (Scopus)

Abstract

Ca2+ has been postulated as a cytosolic second messenger in the regulation of cardiac oxidative phosphorylation. This hypothesis draws support from the well-known effects of Ca2+ on muscle activity, which is stimulated in parallel with the Ca2+-sensitive dehydrogenases (CaDH). The effects of Ca2+ on oxidative phosphorylation were further investigated in isolated porcine heart mitochondria at the level of metabolic driving force (NADH or Δψ) and ATP production rates (flow). The resulting force-flow (F- F) relationships permitted the analysis of Ca2+ effects on several putative control points within oxidative phosphorylation, simultaneously. The F-F relationships resulting from additions of carbon substrates alone provided a model of pure CaDH activation. Comparing this curve with variable Ca2+ concentration ([Ca2+]) effects revealed an approximate twofold higher ATP production rate than could be explained by a simple increase in NADH or Δψ via CaDH activation. The half-maximal effect of Ca2+ at state 3 was 157 nM and was completely inhibited by ruthenium red (1 μM), indicating matrix dependence of the Ca2+ effect. Arsenate was used as a probe to differentiate between F0/F1-ATPase and adenylate translocase activity by a futile recycling of ADP-arsenate within the matrix, catalyzed by the F0/F1-ATPase. Ca2+ increased the ADP arsenylation rate more than twofold, suggesting a direct effect on the F0/F1-ATPase. These results suggest that Ca2+ activates cardiac aerobic respiration at the level of both the CaDH and F0/F1-ATPase. This type of parallel control of both intermediary metabolism and ATP synthesis may provide a mechanism of altering ATP production rates with minimal changes in the high-energy intermediates as observed in vivo.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume278
Issue number2 47-2
StatePublished - 2000
Externally publishedYes

Fingerprint

Proton-Translocating ATPases
Oxidative Phosphorylation
Oxidoreductases
Adenosine Triphosphate
Chemical activation
NAD
Adenosine Diphosphate
Ruthenium Red
Mitochondria
Second Messenger Systems
Metabolism
Muscle
Recycling
Carbon
Flow rate
Heart Mitochondria
Substrates
Respiration
Swine
Muscles

Keywords

  • ATP synthesis
  • Dehydrogenase
  • Force-flow analysis
  • Metabolism

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Ca2+ activation of heart mitochondrial oxidative phosphorylation : Role of the F0/F1-ATPase. / Territo, Paul; Mootha, Vamsi K.; French, Stephanie A.; Balaban, Robert S.

In: American Journal of Physiology - Cell Physiology, Vol. 278, No. 2 47-2, 2000.

Research output: Contribution to journalArticle

Territo, Paul ; Mootha, Vamsi K. ; French, Stephanie A. ; Balaban, Robert S. / Ca2+ activation of heart mitochondrial oxidative phosphorylation : Role of the F0/F1-ATPase. In: American Journal of Physiology - Cell Physiology. 2000 ; Vol. 278, No. 2 47-2.
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