Orphan nuclear receptor estrogen-related receptor α is essential for adaptive themogenesis

Josep A. Villena, M. Benjamin Hock, William Y. Chang, Joanalyn E. Barcas, Vincent Giguère, Anastasia Kralli

Research output: Contribution to journalArticle

Abstract

Survival of organisms requires the ability to adapt to changes in the environment. Adaptation of oxidative metabolism is essential for meeting increased energy demands in response to Stressors, such as exposure to cold temperatures or increased physical activity. Adaptive changes in metabolism are often achieved at the level of gene expression, and nuclear receptors have prevalent roles in mediating such responses. Estrogen-related receptor α(ERRα) was the first orphan nuclear receptor to be identified, and yet its physiologic function remains unknown. Mere, we show that mice lacking ERRα are unable to maintain body temperature when exposed to cold. Surprisingly, the inability to adapt to cold is not due to defects in the acute transcriptional induction of genes important for thermogenesis. Rather, we show that ERRα is needed for the high levels of mitochondria! biogenesis and oxidative capacity characteristic of brown adipose tissue (BAT), and thus for providing the energy necessary for thermogenesis. ERRa fulfills this role by acting directly at genes important for mitochondrial function, parallel to other factors controlling mitochondrial gene expression, such as NRF1 and NRF2/GABPA. Our findings demonstrate that ERRα is a key regulator of mitochondrial biogenesis and oxidative metabolism, and essential for adaptive thermogenesis.

Original languageEnglish (US)
Pages (from-to)1418-1423
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number4
DOIs
StatePublished - Jan 23 2007
Externally publishedYes

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Orphan Nuclear Receptors
Estrogen Receptors
Thermogenesis
Mitochondrial Genes
Gene Expression
Brown Adipose Tissue
Organelle Biogenesis
Cytoplasmic and Nuclear Receptors
Body Temperature
Mitochondria
Genes

Keywords

  • Brown adipose tissue
  • Mitochondrial biogenesis
  • Oxidative metabolism

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Orphan nuclear receptor estrogen-related receptor α is essential for adaptive themogenesis. / Villena, Josep A.; Hock, M. Benjamin; Chang, William Y.; Barcas, Joanalyn E.; Giguère, Vincent; Kralli, Anastasia.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 4, 23.01.2007, p. 1418-1423.

Research output: Contribution to journalArticle

Villena, Josep A. ; Hock, M. Benjamin ; Chang, William Y. ; Barcas, Joanalyn E. ; Giguère, Vincent ; Kralli, Anastasia. / Orphan nuclear receptor estrogen-related receptor α is essential for adaptive themogenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 4. pp. 1418-1423.
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