Estrogen-related receptor α (ERRα) and ERRγ are essential coordinators of cardiac metabolism and function.

Published

Journal Article

Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function.

Full Text

Duke Authors

Cited Authors

  • Wang, T; McDonald, C; Petrenko, NB; Leblanc, M; Wang, T; Giguere, V; Evans, RM; Patel, VV; Pei, L

Published Date

  • April 2015

Published In

Volume / Issue

  • 35 / 7

Start / End Page

  • 1281 - 1298

PubMed ID

  • 25624346

Pubmed Central ID

  • 25624346

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/mcb.01156-14

Language

  • eng