ERRalpha: a metabolic function for the oldest orphan

Trends Endocrinol Metab. 2008 Oct;19(8):269-76. doi: 10.1016/j.tem.2008.07.005. Epub 2008 Sep 6.


Estrogen receptor related receptor (ERR)alpha was one of the first identified (1988) orphan nuclear receptors. Many of the orphan receptors identified after ERRalpha were deorphanized in a timely manner and appreciated as key transcriptional regulators of metabolic pathways. ERRalpha, however, remains an orphan. Nevertheless, recent studies have defined regulatory mechanisms and transcriptional targets of ERRalpha, allowing this receptor to join ranks with other nuclear receptors that control metabolism. Notably, mice lacking ERRalpha show defects when challenged with stressors that require a 'shift of gears' in energy metabolism, such as exposure to cold, cardiac overload or infection. These findings establish the importance of ERRalpha for adaptive energy metabolism, and suggest that strategies targeting ERRalpha may be useful in fighting metabolic diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Energy Metabolism / genetics*
  • Energy Metabolism / physiology
  • Humans
  • Metabolic Networks and Pathways / genetics*
  • Metabolic Networks and Pathways / physiology
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Multigene Family
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / physiology*
  • Trans-Activators / physiology
  • Transcription Factors


  • ERRalpha estrogen-related receptor
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Receptors, Estrogen
  • Trans-Activators
  • Transcription Factors