Cardiac nuclear receptors: architects of mitochondrial structure and function
Rick B. Vega, Daniel P. Kelly
Rick B. Vega, Daniel P. Kelly
Published February 13, 2017
Citation Information: J Clin Invest. 2017;127(4):1155-1164. https://doi.org/10.1172/JCI88888.
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Review Series

Cardiac nuclear receptors: architects of mitochondrial structure and function

Abstract

The adult heart is uniquely designed and equipped to provide a continuous supply of energy in the form of ATP to support persistent contractile function. This high-capacity energy transduction system is the result of a remarkable surge in mitochondrial biogenesis and maturation during the fetal-to-adult transition in cardiac development. Substantial evidence indicates that nuclear receptor signaling is integral to dynamic changes in the cardiac mitochondrial phenotype in response to developmental cues, in response to diverse postnatal physiologic conditions, and in disease states such as heart failure. A subset of cardiac-enriched nuclear receptors serve to match mitochondrial fuel preferences and capacity for ATP production with changing energy demands of the heart. In this Review, we describe the role of specific nuclear receptors and their coregulators in the dynamic control of mitochondrial biogenesis and energy metabolism in the normal and diseased heart.

Authors

Rick B. Vega, Daniel P. Kelly

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Figure 1

Developmental changes in myocardial fuel substrate preference are linked to mitochondrial biogenesis and maturation.

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Developmental changes in myocardial fuel substrate preference are linked...
The fetal heart relies primarily on glucose (glycolysis) and lactate as preferred fuel substrates. In the postnatal period FAO becomes the primary energy-producing process. This is preceded by a burst of mitochondrial biogenesis and mitophagy, events that are required to build an adult mitochondria network with high oxidative and ATP synthetic capacity.