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

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

  • Mol Cell Biol. 2015 Apr;35(7):1281-98. doi: 10.1128/MCB.01156-14.
Ting Wang 1,  Caitlin McDonald 1,  Nataliya B Petrenko 2,  Mathias Leblanc 3,  Tao Wang 2,  Vincent Giguere 4,  Ronald M Evans 5,  Vickas V Patel 2,  Liming Pei 6
Affiliations

Affiliations

  • 1 Center for Mitochondrial and Epigenomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • 2 Penn Cardiovascular Institute and Section of Cardiac Electrophysiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • 3 Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.
  • 4 Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada.
  • 5 Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California, USA.
  • 6 Center for Mitochondrial and Epigenomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA [email protected].
PMID: 25624346 DOI: 10.1128/MCB.01156-14
Abstract

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.

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