Cardiac Energy Metabolism Homeostasis: Role of Cytosolic Calcium

doi:10.1006/jmcc.2002.2082

Journal of Molecular and Cellular Cardiology

Volume 34, Issue 10, October 2002, Pages 1259-1271

https://doi.org/10.1006/jmcc.2002.2082 Get rights and content

Abstract

R. S. Balaban. Cardiac Energy Metabolism Homeotasis: Role of Cytosolic Calcium. Journal of Molecular and Cellular Cardiology (2002) 34, 1259–1271. The heart is capable of dramatically altering its overall energy flux with minimal changes in the concentrations of metabolites that are associated with energy metabolism. This cardiac energy metabolism homeostasis is discussed with regard to the potential cytosolic control network responsible for controlling the major energy conversion pathway, oxidative phosphorylation in mitochondria. Several models for this cytosolic control network have been proposed, but a cytosolic Ca²⁺ dependent parallel activation scheme for metabolism and work is consistent with most of the experimental results. That model proposes that cytosolic Ca²⁺ regulates both the utilization of ATP by the work producing ATPases as well as the mitochondrial production of ATP. Recent studies have provided evidence supporting this role of cytosolic Ca²⁺. These data include the demonstration that mitochondrial [Ca²⁺] can track cytosolic [Ca²⁺] and that the compartmentation of cytosolic [Ca²⁺] can facilitate this process. On the metabolic side, Ca²⁺ has been shown to rapidly activate several steps in oxidative phosphorylation, including F₁F₀-ATPase ATP production as well as several dehydrogenases, which results in a homeostasis of mitochondrial metabolites similar to that observed in the cytosol. Numerous problems with the Ca²⁺ parallel activation hypothesis remain including the lack of specific mechanisms of mitochondrial Ca²⁺ transport and regulation of F₁F₀-ATPase, the time dependence of Ca²⁺ activation of cytosolic ATPases as well as oxidative phosphorylation, and the role of cytosolic compartmentation. In addition, the lack of cytosolic or mitochondrial [Ca²⁺] measurements under in vivo conditions is problematic. Several lines of investigation to address these issues are suggested. A model of the cardiac energy metabolism control network is proposed that includes a Ca²⁺ parallel activation component together with more classical elements including metabolite feedback and cytosolic compartmentation.

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^f1: Please address all correspondence to: Robert S. Balaban, Laboratory of Cardiac Energetics National Heart Lung and Blood Institute, Building 10, Room B1 D161, Bethesda, MD 20892-0001, USA. Tel: 301-496-3658; Fax: 301-402-2389; E-mail:[email protected]

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Myocardial Energy Metabolism in Health and DiseaseCardiac Energy Metabolism Homeostasis: Role of Cytosolic Calcium

Abstract

Int Rev Cytol

J Mol Cell Cardiol

Biophys J

Cell Calcium

Biochimica et Biophysica Acta

FEBS Lett

Cell Calcium

J Mol Cell Cardiol

Biophys J

Biochim Biophys Acta

J Biol Chem

Biophys J

J Biol Chem

FEBS Lett

Biochem Biophys Res Commun

FEBS Lett

Biochim Biophys Acta

Biochim Biophys

J Mol Cell Cardiol

J Mol Cell Cardiol

Biophys J

FEBS Lett

J Biol Chem

Trends Cardiovasc Med

J Biol Chem

The simultaneous symbiotic origin of mitochondria, cholorplasts, and mircobodies

Ann N Y Acad Sci

Maximum oxidative phosphorylation capacity of the mammalian heart

Am J Physiol

Relation between work and labile phosphate content in the isolated dog heart

Circ Res

High-energy phosphate concentrations in dog myocardium during stress

Am J Physiol

The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart

Biochem J

Relation between work and phosphate metabolite in the in vivo paced mammalian heart

Science

Regulation of the oxidative phosphorylation rate in the intact cell

Biochemistry

Transmural high energy phosphate distribution and response to alterations in workload in the normal canine myocardium as studied with spatially localized 31P NMR spectroscopy

Mag Res Med

Relation between phosphate metabolites and oxygen consumption of heart in vivo

Am J Physiol

Cardiac transfer function relating energy metabolism to workload in different species as studied with 31P NMR

Mag Res Med

Metabolic response of the human heart to inotropic stimulation: in vivo phosphorus-31 studies of normal and cardiomyopathic myocardium

Mag Res Med

Regional myocardial metabolism of high-energy phosphates during isometric exercise in patients with coronary artery disease

N Engl J Med

Metabolic response of normal human myocardium to high-dose atropine-dobutamine stress studied by 31P-MRS

Circulation

Effects of afterload and heart rate on NAD(P)H redox state in the isolated rabbit heart

Am J Physiol

Effects of cardiac work on electrical potential gradient across mitochondrial membrane in perfused rat hearts

Am J Physiol

Increase of cardiac work is associated with decrease of mitochondrial NADH

Am J Physiol

Transmural bioenergetic responses of normal myocardium to high workstates

Am J Physiol

Phosphorus-31 nuclear magnetic resonance analysis of transient changes of canine myocardial metabolism in vivo

J Clin Invest

How phosphocreatine buffers cyclic changes in ATP demand in working muscle

Adv Exp Med Biol

Some new aspects of creatine kinase (CK): compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology

Biofactors

Myocardial Energy Metabolism in Health and Disease
Cardiac Energy Metabolism Homeostasis: Role of Cytosolic Calcium