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Circ Res. 2014 Feb 14;114(4):717-29. doi: 10.1161/CIRCRESAHA.114.301863.

Matrix revisited: mechanisms linking energy substrate metabolism to the function of the heart.

Author information

1
From the Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago IL (A.N.C., E.D.L.); and Department of Internal Medicine, Division of Cardiology, The University of Texas Medical School at Houston (H.T.).

Abstract

Metabolic signaling mechanisms are increasingly recognized to mediate the cellular response to alterations in workload demand, as a consequence of physiological and pathophysiological challenges. Thus, an understanding of the metabolic mechanisms coordinating activity in the cytosol with the energy-providing pathways in the mitochondrial matrix becomes critical for deepening our insights into the pathogenic changes that occur in the stressed cardiomyocyte. Processes that exchange both metabolic intermediates and cations between the cytosol and mitochondria enable transduction of dynamic changes in contractile state to the mitochondrial compartment of the cell. Disruption of such metabolic transduction pathways has severe consequences for the energetic support of contractile function in the heart and is implicated in the pathogenesis of heart failure. Deficiencies in metabolic reserve and impaired metabolic transduction in the cardiomyocyte can result from inherent deficiencies in metabolic phenotype or maladaptive changes in metabolic enzyme expression and regulation in the response to pathogenic stress. This review examines both current and emerging concepts of the functional linkage between the cytosol and the mitochondrial matrix with a specific focus on metabolic reserve and energetic efficiency. These principles of exchange and transport mechanisms across the mitochondrial membrane are reviewed for the failing heart from the perspectives of chronic pressure overload and diabetes mellitus.

KEYWORDS:

cytosol; diabetes mellitus; heart failure; metabolic pathways; metabolism; mitochondria; mobilization

PMID:
24526677
PMCID:
PMC4410983
DOI:
10.1161/CIRCRESAHA.114.301863
[Indexed for MEDLINE]
Free PMC Article

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