February 1, 2000AJP Cell Physiology
Ca2+ activation of heart mitochondrial oxidative phosphorylation: role of the F0/F1-ATPase
Population
Isolated porcine heart mitochondria
Comparison
Variable Ca2+ concentrations vs Carbon substrates alone
Design
Preclinical
Authors
Discussion
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Implication
May extend Ca2+ targets to F0/F1-ATPase in cardiac mitochondria; leaves open human translation and clinical relevance.
Key Points
- To determine whether calcium stimulates cardiac mitochondrial oxidative phosphorylation solely through calcium-sensitive dehydrogenases or also through direct action on the F0/F1-ATPase.
- Assessed metabolic driving forces (NADH and membrane potential) versus ATP synthesis rates using force-flow relationships in isolated porcine heart mitochondria.
- Tested mitochondrial matrix calcium dependence with ruthenium red and measured direct F0/F1-ATPase activity via an arsenate-mediated ADP-arsenylation futile cycle.
- Calcium increased ATP production rates approximately twofold higher than could be explained by dehydrogenase activation alone, with a half-maximal effect at 157 nM in state 3 that was completely inhibited by 1 µM ruthenium red.
- Calcium increased the ADP arsenylation rate by more than twofold, confirming a direct activating effect on the F0/F1-ATPase.
Structured PICO
P
Population
Isolated porcine heart mitochondria
I
Intervention
Variable Ca2+ concentrations
C
Comparator
Carbon substrates alone (model of pure CaDH activation)
O
Outcome
ATP production rates (flow) and metabolic driving force (NADH or Deltapsi)surrogate
Ca2+ activates cardiac aerobic respiration at the level of both the Ca-sensitive dehydrogenases and F0/F1-ATPase, providing a mechanism for altering ATP production rates with minimal changes in high-energy intermediates.
Cite This Study
Territo et al. (2000) studied this question.