title: ERRalpha: a metabolic function for the oldest orphan.
abstract: 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.
authors.affiliation: Institut de Recerca Hospital Universitari Vall d'Hebron, Grup de Metabolisme i Obesitat, Barcelona, Spain.
authors.forename: Josep A
authors.initials: JA
authors.lastname: Villena
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kralli
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000235:genetics* / Q000502:physiology; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D005810:Multigene Family; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C485290:Ppargc1a protein, mouse
references.citation: Trends Endocrinol Metab. 2006 May-Jun;17(4):166-71
references.pmid: 16580224
references.citation: J Clin Invest. 2006 Jan;116(1):125-36
references.pmid: 16374519
references.citation: Mol Endocrinol. 2008 Mar;22(3):570-84
references.pmid: 18063693
references.citation: Diabetes. 2006 Jun;55(6):1783-91
references.pmid: 16731843
references.citation: J Med Chem. 2007 Dec 27;50(26):6722-4
references.pmid: 18052088
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8912-7
references.pmid: 15184675
references.citation: J Biol Chem. 2002 Dec 27;277(52):50991-5
references.pmid: 12397057
references.citation: Mol Cell Biol. 2004 Oct;24(20):9079-91
references.pmid: 15456881
references.citation: J Physiol. 2005 Aug 15;567(Pt 1):349-58
references.pmid: 15961417
references.citation: FEBS J. 2006 Apr;273(8):1669-80
references.pmid: 16623704
references.citation: Endocr Relat Cancer. 2006 Dec;13 Suppl 1:S25-32
references.pmid: 17259555
references.citation: Biochem Biophys Res Commun. 2007 Jul 6;358(3):813-8
references.pmid: 17512501
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8466-71
references.pmid: 12832613
references.citation: Cell. 1995 Dec 15;83(6):835-9
references.pmid: 8521507
references.citation: Endocr Rev. 2006 Dec;27(7):728-35
references.pmid: 17018837
references.citation: Cancer Res. 2005 Jul 15;65(14):6120-9
references.pmid: 16024613
references.citation: Cell Metab. 2007 Jul;6(1):25-37
references.pmid: 17618854
references.citation: Biochem Biophys Res Commun. 2007 May 25;357(1):231-6
references.pmid: 17418099
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6472-7
references.pmid: 15087503
references.citation: J Biol Chem. 2004 Dec 10;279(50):52052-8
references.pmid: 15466464
references.citation: Mol Cell Biol. 1997 Sep;17(9):5400-9
references.pmid: 9271417
references.citation: J Biol Chem. 2003 Mar 14;278(11):9013-8
references.pmid: 12522104
references.citation: Genes Dev. 2007 Aug 1;21(15):1909-20
references.pmid: 17671090
references.citation: Mol Cell. 2002 Feb;9(2):303-13
references.pmid: 11864604
references.citation: Science. 2001 Nov 30;294(5548):1866-70
references.pmid: 11729302
references.citation: J Biol Chem. 2006 Dec 29;281(52):39897-906
references.pmid: 17079227
references.citation: Biochemistry. 2007 Aug 28;46(34):9795-804
references.pmid: 17676930
references.citation: Mol Cell Biol. 2000 Mar;20(5):1868-76
references.pmid: 10669761
references.citation: Mol Endocrinol. 2006 Feb;20(2):302-10
references.pmid: 16150865
references.citation: J Med Chem. 2004 Nov 4;47(23):5593-6
references.pmid: 15509154
references.citation: Trends Endocrinol Metab. 2006 Aug;17(6):243-50
references.pmid: 16815031
references.citation: Trends Endocrinol Metab. 2002 Jul;13(5):220-5
references.pmid: 12185669
references.citation: Cell. 2006 Jun 30;125(7):1241-52
references.pmid: 16814712
references.citation: Curr Top Med Chem. 2006;6(3):203-15
references.pmid: 16515477
references.citation: Cell Metab. 2007 May;5(5):345-56
references.pmid: 17488637
references.citation: Mol Cell Biol. 2003 Nov;23(22):7947-56
references.pmid: 14585956
references.citation: Mol Cancer Res. 2007 Jan;5(1):71-85
references.pmid: 17259347
references.citation: Nature. 1988 Jan 7;331(6151):91-4
references.pmid: 3267207
references.citation: Mol Endocrinol. 1997 Mar;11(3):342-52
references.pmid: 9058380
references.citation: Mol Cell. 2006 Dec 8;24(5):797-803
references.pmid: 17157261
references.citation: Nat Genet. 2003 Jul;34(3):267-73
references.pmid: 12808457
references.citation: J Biol Chem. 2004 Apr 30;279(18):18504-10
references.pmid: 14978033
references.citation: J Biol Chem. 1997 Dec 12;272(50):31693-9
references.pmid: 9395511
references.citation: J Biol Chem. 2002 Apr 19;277(16):13918-25
references.pmid: 11854298
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1418-23
references.pmid: 17229846
references.citation: J Clin Invest. 2006 Mar;116(3):615-22
references.pmid: 16511594
references.citation: Nature. 2006 Oct 19;443(7113):787-95
references.pmid: 17051205
references.citation: J Biol Chem. 2007 Aug 10;282(32):23231-9
references.pmid: 17556356
references.citation: J Clin Endocrinol Metab. 2005 May;90(5):3115-21
references.pmid: 15713703
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12378-83
references.pmid: 14530391
references.citation: J Biol Chem. 2006 Jan 6;281(1):99-106
references.pmid: 16267049
references.citation: Mol Endocrinol. 2007 Jan;21(1):62-76
references.pmid: 17053040
references.citation: Mol Cell Biol. 2005 Dec;25(24):10684-94
references.pmid: 16314495
references.citation: J Biol Chem. 2002 Oct 25;277(43):40265-74
references.pmid: 12181319
references.citation: J Biol Chem. 2004 Nov 19;279(47):49330-7
references.pmid: 15337744
references.citation: Cell. 2006 Nov 3;127(3):465-8
references.pmid: 17081970
references.citation: J Mol Endocrinol. 2005 Apr;34(2):473-87
references.pmid: 15821111
references.citation: J Mol Endocrinol. 2003 Dec;31(3):349-57
references.pmid: 14664699
references.citation: Mol Endocrinol. 2006 May;20(5):1035-47
references.pmid: 16439465
references.citation: J Biol Chem. 2006 Oct 27;281(43):32140-7
references.pmid: 16923809
references.citation: Science. 1999 Apr 30;284(5415):757-60
references.pmid: 10221899
references.citation: J Biol Chem. 2000 May 26;275(21):16302-8
references.pmid: 10748020
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9713-8
references.pmid: 11481440
references.citation: Mol Endocrinol. 1990 Mar;4(3):363-9
references.pmid: 2188115
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6570-5
references.pmid: 15100410
references.citation: Genes Dev. 2004 Feb 15;18(4):357-68
references.pmid: 15004004