ERRα: a metabolic function for the oldest orphan
Open accessAbstract
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.
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HIF-1α is a key factor in suppressing mitochondrial biogenesis and PGC-1α expression through negative regulation of MYC and MYC-dependent transcription factors (PPARs and ERRs) that activate the PGC-1α gene.
“HIF-1α is also a key factor in suppressing mitochondrial biogenesis and PGC-1α expression through mechanisms of negative regulation of the transcription factor MYC and the MYC-dependent transcription factors (PPARs and ERRs) that activate the PGC-1α gene [14,86,87].”
From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [14]
The sections on regulation and cellular function of ERRα (page not specified) link PGC-1α and ERRα to mitochondrial biogenesis. They do not establish the attributed mechanism: HIF-1α suppressing MYC, MYC-dependent PPARs or ERRs activating the PGC-1α gene, or the resulting suppression of PGC-1α expression. The paper instead describes PGC-1α as regulating ERRα expression and ERRα as a downstream effector of PGC-1α. (LLM, conf=0.78)
Experimental — accuracy not yet measuredImprovement of microcirculation and penumbral tissue oxygenation mediated by Mexidol and Semax may be crucial to reverse the HIF-1α-dependent blockade of PGC-1α expression.
“Improvement of microcirculation and penumbral tissue oxygenation mediated by the drugs Mexidol and Semax may be crucial to reverse the HIF-1α-dependent blockade of PGC-1α expression [14,86,87].”
From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [14]
The section ‘Regulation of ERRα: the roles of PGC-1α and PGC-1β’ discusses PGC-1α in energy metabolism, but does not address HIF-1α-dependent suppression of its expression. Searches for HIF-1α, hypoxia, oxygenation, Mexidol, Semax, and penumbral microcirculation found no passage supporting the proposed mechanism; page numbers were unavailable in our copy. (LLM, conf=0.75)
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Cites
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“RIP140 acts as the antithesis of PGC-1α, suppressing many of the energy metabolism genes that PGC-1α activates [55] (Figure 1).”
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“Additional signals are likely to impact ERRα function via other mechanisms, including ERRα phosphorylation and sumoylation [36-39].”
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“Additional signals are likely to impact ERRα function via other mechanisms, including ERRα phosphorylation and sumoylation [36-39].”
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“A different mode of repression has been shown in the case of the gluconeogenic/ glyceroneogenic gene PEPCK, where ERRα binding at a complex response element inhibits PGC-1α recruitment and PEPCK induction [56].”
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“Additional signals are likely to impact ERRα function via other mechanisms, including ERRα phosphorylation and sumoylation [36-39].”
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“by ERRα promoting adipogenesis [60], might underlie some of the phenotypes in the ERRα null mice.”
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“Such studies have been covered in other reviews [6-10] and will not be discussed here.”
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“Collectively, these and later studies have established that ERRα activated by PGC-1α or PGC-1β induces genes with roles in lipid transport [42,43], fatty acid oxidation [24,26,29,41-44], TCA cycle [24,41,44-46], oxidative phosphorylation [26,29,41,42,44-46], mitochondrial biogenesis [26,44], mitochondrial dynamics [35…”
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“Furthermore, the functional significance of some of these ERREs has been validated in vitro by showing that these response elements confer ERRα- and PGC-1α-dependent regulation of reporter genes in transfection assays [26,42,43,47-51].”
BackgroundRIP140 Expression Is Stimulated by Estrogen-related Receptor α during Adipogenesis
Nichol, D., Christian, M., Steel, J. H., White, R., & Parker, M. G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604803200 · Cited by 61 · see citing works
Phosphorylation-Dependent Sumoylation of Estrogen-Related Receptor α1
Vu, E. H., Kraus, R. J., & Mertz, J. E. (2007) · Biochemistry · doi:10.1021/bi700316g · Cited by 59 · cited 1× · see citing works
“Additional signals are likely to impact ERRα function via other mechanisms, including ERRα phosphorylation and sumoylation [36-39].”
BackgroundDefinition of the Molecular Basis for Estrogen Receptor-Related Receptor-α-Cofactor Interactions
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Liu, D., Zhang, Z., & Teng, C. T. (2005) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01586 · Cited by 56 · see citing works
Barry, J. B., Laganière, J., & Giguère, V. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0313 · Cited by 50 · cited 1× · see citing works
“One possibility is that the sequence of the PEPCK ERRE and/or the proximity to other elements directs ERRα binding as a monomer, which cannot recruit PGC-1α [36,57].”
BackgroundJohnston, S. D. (1997) · Molecular Endocrinology · doi:10.1210/me.11.3.342 · Cited by 44 · see citing works
Studying non-mammalian models? Not a fool's ERRand!
Bardet, P., Laudet, V., & Vanacker, J.-M. (2006) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2006.03.005 · Cited by 38 · cited 1× · see citing works
“Such studies have been covered in other reviews [6-10] and will not be discussed here.”
BackgroundOn the Intractability of Estrogen-Related Receptor α as a Target for Activation by Small Molecules
Hyatt, S. M., Lockamy, E. L., Stein, R. A., McDonnell, D. P., Miller, A. B., Orband‐Miller, L. A., Willson, T. M., & Zuercher, W. J. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm7012387 · Cited by 30 · cited 1× · see citing works
“For ERRα in particular, screening and structure-guided design efforts have identified synthetic inverse agonists that inhibit ERRα function, but no agonists, suggesting that ERRα may stay an orphan [14-17].”
Background
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Research works printed but not linked: 2
- [15]Willy PJ Regulation of PPARgamma coactivator 1alpha (PGC-1alpha) signaling by an estrogen-related receptor alpha (ERRalpha) ligand Proc. Natl. Acad. Sci. U. S. A 2004 101 8912 8917 15184675 PMC428446
- [26]Schreiber SN The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis Proc. Natl. Acad. Sci. U. S. A 2004 101 6472 6477 15087503 PMC404069
Cited by
Sorted by citations
Immunometabolism governs dendritic cell and macrophage function
O'Neill, L. A. J., & Pearce, E. J. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20151570 · Cited by 1,715 · see citing works
Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network
Scarpulla, R. C. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.09.019 · Cited by 1,281 · see citing works
Metabolic Regulation of T Lymphocytes
MacIver, N. J., Michalek, R. D., & Rathmell, J. C. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095956 · Cited by 1,244 · see citing works
“The estrogen-related receptors (ERRα, β, and γ; NR3B1, 2, and 3, respectively) are a subfamily of nuclear receptors with established roles in regulating both glycolytic and mitochondrial metabolic pathways (39, 40).”
BackgroundRegulation of energy metabolism by long-chain fatty acids
Nakamura, M., Yudell, B. E., & Loor, J. J. (2013) · Progress in Lipid Research · doi:10.1016/j.plipres.2013.12.001 · Cited by 829 · see citing works
“Thus, NRF1,2 and ERRa are likely key mediators of mitochondrial biogenesis in skeletal muscle in response to endurance exercise.”
InfluentialTranscriptional Control of Mitochondrial Biogenesis and Function
Hock, M. B., & Kralli, A. (2009) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163119 · Cited by 616 · see citing works
“PGC-1α also led to the identification of related coactivators [PGC-1β and the PGC-1-related coactivator (PRC)] and other transcription factors [the nuclear receptors ERRs (estrogen-related receptors)] that function in the same or similar pathways (9, 10).”
BackgroundInfluentialSelf-citationPTEN: Tumor Suppressor and Metabolic Regulator
Chen, C.-Y., Chen, J., He, L., & Stiles, B. L. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00338 · Cited by 589 · see citing works
“The best characterized isoform of ERRs, ERRα is abundantly expressed in high oxidative organs and recognized as a key regulators of adaptive energy metabolism (122).”
BackgroundMetabolic switching and fuel choice during T‐cell differentiation and memory development
van der Windt, G. J. W., & Pearce, E. L. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01150.x · Cited by 563 · see citing works
“Another important regulator of transcription of metabolic genes is the nuclear hormone receptor, estrogen-related receptor-a (ERR-a) (91, 92) (Fig.”
Vascular endothelial growth factor B controls endothelial fatty acid uptake
Hagberg, C. E., Falkevall, A., Wang, X., Larsson, E., Huusko, J., Nilsson, I., van Meeteren, L. A., Samén, E., Lu, L., Vanwildemeersch, M., et al. (2010) · Nature · doi:10.1038/nature08945 · Cited by 514 · see citing works
Metabolic pathways in T cell fate and function
Gerriets, V. A., & Rathmell, J. C. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.01.010 · Cited by 425 · see citing works
PGC-1 Coactivators in Cardiac Development and Disease
Rowe, G. C., Jiang, A., & Arany, Z. P. (2010) · Circulation Research · doi:10.1161/circresaha.110.223818 · Cited by 355 · see citing works
Emerging concepts of T cell metabolism as a target of immunotherapy
Chang, C., & Pearce, E. L. (2016) · Nature Immunology · doi:10.1038/ni.3415 · Cited by 337 · see citing works
Muscle as a “Mediator” of Systemic Metabolism
Baskin, K. K., Winders, B. R., & Olson, E. N. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.021 · Cited by 333 · see citing works
“Mouse gene deletion studies have revealed a role for ERRa in regulation of cardiac energy metabolism and adaptation to pressure overload (Huss et al., 2007; Huss and Kelly, 2004; Villena and Kralli, 2008).”
BackgroundNew aspects of the Warburg effect in cancer cell biology
Bensinger, S. J., & Christofk, H. R. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.02.003 · Cited by 309 · see citing works
NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function
Yamamoto, H., Williams, E. G., Mouchiroud, L., Cantó, C., Fan, W., Downes, M., Héligon, C., Barish, G. D., Desvergne, B., Evans, R. M., et al. (2011) · Cell · doi:10.1016/j.cell.2011.10.017 · Cited by 261 · see citing works
“Amongst the ERRs, mainly ERRα and ERRγ seem to be involved in the coordination of muscle energy homeostasis [reviewed in (Giguere, 2008; Villena and Kralli, 2008)].”
InfluentialHeterogeneity in Cancer Metabolism: New Concepts in an Old Field
Gentric, G., Mieulet, V., & Mechta‐Grigoriou, F. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6750 · Cited by 237 · see citing works
Palamiuc, L., Schlagowski, A.-I., Ngo, S. T., Vernay, A., Dirrig‐Grosch, S., Henriques, A., Boutillier, A., Zoll, J., Echaniz‐Laguna, A., Loeffler, J., et al. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201404433 · Cited by 235 · see citing works
“…of the disease the decrease in PGC-1a protein levels correlated with a decrease in the mRNA expression of the main target genes of PGC-1a pathway, estrogen-related receptor a (ERRa), mitofusin 2 (Mfn2), and nuclear respiratory factor 1 (Nrf1) (Puigserver, 2005; Villena & Kralli, 2008) (Fig 5E).”
Oestrogen-related receptors in breast cancer: control of cellular metabolism and beyond
Deblois, G., & Giguère, V. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3396 · Cited by 226 · see citing works
FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity
Wang, X. X., Wang, D., Luo, Y., Myakala, K., Dobrinskikh, E., Rosenberg, A. Z., Levi, J., Kopp, J. B., Field, A. P., Hill, A., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2017020222 · Cited by 226 · see citing works
Michalek, R. D., Gerriets, V. A., Nichols, A. G., Inoue, M., Kazmin, D., Chang, C.-Y., Dwyer, M. A., Nelson, E. R., Pollizzi, K. N., Ilkayeva, O., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108856108 · Cited by 216 · see citing works
G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and Diabetes
Wang, X. X., Herman‐Edelstein, M., Gafter, U., Qiu, L., Luo, Y., Dobrinskikh, E., Lucia, S. M., Adorini, L., D’Agati, V. D., Levi, J., et al. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014121271 · Cited by 211 · see citing works
Estrogen Signaling in Metabolic Inflammation
Monteiro, R., Teixeira, D., & Calhau, C. (2014) · Mediators of Inflammation · doi:10.1155/2014/615917 · Cited by 211 · see citing works
An Acetylation Switch Modulates the Transcriptional Activity of Estrogen-Related Receptor α
Wilson, B. J., Tremblay, A. M., Deblois, G., Sylvain-Drolet, G., & Giguère, V. (2010) · Molecular Endocrinology · doi:10.1210/me.2009-0441 · Cited by 192 · see citing works
The PGC-1/ERR signaling axis in cancer
Deblois, G., St‐Pierre, J., & Giguère, V. (2012) · Oncogene · doi:10.1038/onc.2012.529 · Cited by 182 · see citing works
Audet‐Walsh, É., & Giguère, V. (2014) · Acta Pharmacologica Sinica · doi:10.1038/aps.2014.121 · Cited by 175 · see citing works
Insulin resistance and altered systemic glucose metabolism in mice lacking Nur77
Chao, L. C., Wroblewski, K., Zhang, Z., Pei, L., Vergnes, L., Ilkayeva, O. R., Ding, S. Y., Reue, K., Watt, M. J., Newgard, C. B., et al. (2009) · Diabetes · doi:10.2337/db09-0763 · Cited by 154 · see citing works
Chaveroux, C., Eichner, L. J., Dufour, C. R., Shatnawi, A. A., Khoutorsky, A., Bourque, G., Sonenberg, N., & Giguère, V. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.003 · Cited by 153 · see citing works
“Estrogen-related receptor a (ERRa, NR3B1) is an orphan nuclear receptor that plays a crucial role in the transcriptional control of mitochondrial function and energy metabolism (Deblois and Giguère, 2011; Eichner and Giguère, 2011; Giguère, 2008; Villena and Kralli, 2008).”
BackgroundPatch, R. J., Searle, L. L., Kim, A. J., De, D., Zhu, X., Askari, H. B., O’Neill, J. C., Abad, M. C., Rentzeperis, D., Liu, J., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm101063h · Cited by 141 · see citing works
Dwyer, M. A., Joseph, J. D., Wade, H. E., Eaton, M. L., Kunder, R. S., Kazmin, D. A., Chang, C., & McDonnell, D. P. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0226 · Cited by 140 · see citing works
Functional and physiological genomics of estrogen-related receptors (ERRs) in health and disease
Deblois, G., & Giguère, V. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.12.009 · Cited by 135 · see citing works
“Since several recent reviews have described in details the origin, biological, and functional properties of the ERRs [2–5], only salient features of these receptors related to the subject of this review will be presented herein.”
BackgroundYuk, J., Kim, T. S., Kim, S. Y., Lee, H., Han, J., Dufour, C. R., Kim, J. K., Jin, H. S., Yang, C., Park, K.-S., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.07.003 · Cited by 134 · see citing works
“ERRa was the first identified orphan nuclear receptor, with a crucial role in regulating energy metabolism and mitochondrial biogenesis (Deblois and Giguère, 2011; Villena and Kralli, 2008).”
BackgroundSingh, B. K., Sinha, R. A., Tripathi, M., Mendoza, A., Ohba, K., Sy, J. A. C., Xie, S. Y., Zhou, J., Ho, J. P., Chang, C.-Y., et al. (2018) · Science Signaling · doi:10.1126/scisignal.aam5855 · Cited by 145 · see citing works
Wang, T., McDonald, C., Petrenko, N. B., Leblanc, M., Wang, T., Giguère, V., Evans, R. M., Patel, V. V., & Pei, L. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.01156-14 · Cited by 131 · see citing works
“In addition, ERR transcriptional activity can be modulated by multiple signaling pathways that reflect either cellular physiological/energy status or metabolic demand from distinct cellular functions (17, 18).”
BackgroundMYC-dependent oxidative metabolism regulates osteoclastogenesis via nuclear receptor ERRα
Bae, S., Lee, M. J., Mun, S. H., Γιαννοπούλου, Ε., Yong‐Gonzalez, V., Cross, J. R., Murata, K., Giguère, V., van der Meulen, M. C. H., & Park‐Min, K. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89935 · Cited by 120 · see citing works
“ERRα transcriptionally regulates the expression of genes encoding energy metabolism regulators (28, 30, 31).”
BackgroundFenofibrate Improves Renal Lipotoxicity through Activation of AMPK-PGC-1α in db/db Mice
Hong, Y. A., Lim, J. H., Kim, M. Y., Kim, T. W., Kim, Y., Yang, K. S., Park, H. S., Choi, S. R., Chung, S., Kim, H. W., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096147 · Cited by 118 · see citing works
Cho, Y., Hazen, B. C., Russell, A. P., & Kralli, A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.489674 · Cited by 113 · see citing works
“ERR and the related receptors ERR and ERR are orphan nuclear receptors that act both downstream and parallel to PGC-1 coactivators to control the expression of a broad set of genes important for energy homeostasis, including genes for mitochondrial biogenesis and oxidative function (30, 31).”
BackgroundSelf-citationGenomic Convergence among ERRα, PROX1, and BMAL1 in the Control of Metabolic Clock Outputs
Dufour, C. R., Levasseur, M.-P., Pham, N. H. H., Eichner, L. J., Wilson, B. J., Charest-Marcotte, A., Duguay, D., Poirier-Héon, J.-F., Cermakian, N., & Giguère, V. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002143 · Cited by 102 · see citing works
ERRα induces H3K9 demethylation by LSD1 to promote cell invasion
Carnesecchi, J., Forcet, C., Zhang, L., Tribollet, V., Barenton, B., Boudra, R., Cerutti, C., Billas, I. M. L., Sérandour, A. A., Carroll, J. S., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1614664114 · Cited by 102 · see citing works
Tripathi, M., Yen, P. M., & Singh, B. K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051645 · Cited by 98 · see citing works
Molecular profiling of dilated cardiomyopathy that progresses to heart failure
Burke, M. A., Chang, S., Wakimoto, H., Gorham, J., Conner, D. A., Christodoulou, D. C., Parfenov, M. G., DePalma, S. R., Eminaga, S., Konno, T., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.86898 · Cited by 96 · see citing works
“Cardiomyocytes displayed a marked shift in metabolic gene transcription: downregulation of aerobic respiration and subsequent upregulation of glucose utilization, changes coincident with attenuated expression of PPARα and PPARγ coactivators -1α (PGC1α) and -1β, and increased expression of the metabolic regulator T-box…”
BackgroundInfluentialERRα as a Bridge Between Transcription and Function: Role in Liver Metabolism and Disease
Xia, H., Dufour, C. R., & Giguère, V. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00206 · Cited by 94 · see citing works
Audet‐Walsh, É., Papadopoli, D. J., Gravel, S., Yee, T., Bridon, G., Caron, M., Bourque, G., Giguère, V., & St‐Pierre, J. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.086 · Cited by 94 · see citing works
“The orphan nuclear receptor known as estrogen-related receptor a (ERRa, NR3B1) and the peroxisome proliferator-activated receptor g co-activator 1a (PGC-1a) act together as a transcriptional regulatory node important for the expression of metabolic genes (Deblois et al., 2013; Giguère, 2008; Mootha et al., 2004; Ville…”
BackgroundGDF15 is a heart‐derived hormone that regulates body growth
Wang, T., Liu, J., McDonald, C., Lupino, K., Zhai, X., Wilkins, B. J., Hakonarson, H. H., & Pei, L. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707604 · Cited by 92 · see citing works
Nuclear Receptors in Bone Physiology and Diseases
Imai, Y., Youn, M., Inoue, K., Takada, I., Kouzmenko, A., & Kato, S. (2013) · Physiological Reviews · doi:10.1152/physrev.00008.2012 · Cited by 89 · see citing works
Hu, X., Xu, X. Y., Lu, Z., Zhang, P., Fassett, J. T., Zhang, Y., Xin, Y., Hall, J. L., Viollet, B., Bache, R. J., et al. (2011) · Hypertension · doi:10.1161/hypertensionaha.111.174128 · Cited by 88 · see citing works
Pardo, R., Enguix, N., Lasheras, J., Felíu, J. E., Kralli, A., & Villena, J. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026989 · Cited by 85 · see citing works
Self-citationKim, S. Y., Yang, C., Lee, H., Kim, J. K., Kim, Y. S., Kim, Y.-R., Js, K., Kim, T. S., Yuk, J., Dufour, C. R., et al. (2017) · Autophagy · doi:10.1080/15548627.2017.1339001 · Cited by 81 · see citing works
Yang, M., Liu, Q., Huang, T., Tan, W., Qu, L., Chen, T., Pan, H., Chen, L., Liu, J., Wong, C., et al. (2020) · Theranostics · doi:10.7150/thno.47037 · Cited by 85 · see citing works
“Estrogen-related receptor alpha (ERRα) is a nuclear hormone receptor that governs the expression of target genes involved in numerous metabolic pathways including those guiding mitochondrial oxidative phosphorylation and lipid metabolism [25].”
Podocyte energy metabolism and glomerular diseases
Imasawa, T., & Rossignol, R. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.06.013 · Cited by 84 · see citing works
HDAC8 substrates: Histones and beyond
Wolfson, N. A., Pitcairn, C. A., & Fierke, C. A. (2012) · Biopolymers · doi:10.1002/bip.22135 · Cited by 82 · see citing works
Androgen-Dependent Repression of ERRγ Reprograms Metabolism in Prostate Cancer
Audet‐Walsh, É., Yee, T., McGuirk, S., Vernier, M., Ouellet, C., St‐Pierre, J., & Giguère, V. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-1204 · Cited by 82 · see citing works
“It has been well demonstrated that ERRα and γ function as integral regulators of cellular energy metabolism (8,15,44).”
BackgroundThe Warburg effect: molecular aspects and therapeutic possibilities
Ngo, H. G., Tortorella, S. M., Ververis, K., & Karagiannis, T. C. (2014) · Molecular Biology Reports · doi:10.1007/s11033-014-3764-7 · Cited by 81 · see citing works
Deblois, G., Chahrour, G., Perry, M.-C., Sylvain-Drolet, G., Muller, W. J., & Giguère, V. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2840 · Cited by 81 · see citing works
Tiraby, C., Hazen, B. C., Gantner, M. L., & Kralli, A. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-1315 · Cited by 79 · see citing works
Self-citationChang, C., & McDonnell, D. P. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3221 · Cited by 79 · see citing works
Giguère, V. (2018) · FEBS Journal · doi:10.1111/febs.14384 · Cited by 77 · see citing works
Saito, K., & Cui, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041091 · Cited by 76 · see citing works
“Indeed, it has been postulated that, rather than in a baseline condition, the roles ERRα plays become more apparent when animals are subjected to various physiological and environmental challenges requiring them to make adaptive responses [102].”
BackgroundEstrogen-Related Receptors in Breast Cancer and Prostate Cancer
Misawa, A., & Inoue, S. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00083 · Cited by 76 · see citing works
Contribution of Impaired Insulin Signaling to the Pathogenesis of Diabetic Cardiomyopathy
Zamora, M., & Villena, J. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112833 · Cited by 74 · see citing works
“Both ERRs and PPARα are well-known regulators of oxidative metabolism by regulating, among others, the expression of genes involved in fatty acid catabolism [61,62].”
BackgroundSelf-citationBisphenol A Exposure Is Associated with in Vivo Estrogenic Gene Expression in Adults
Melzer, D. R., Harries, L. W., Cipelli, R., Henley, W., Money, C., McCormack, P., Young, A., Guralnik, J. M., Ferrucci, L., Bandinelli, S., et al. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1103809 · Cited by 74 · see citing works
Peng, L., Gao, X., Duan, L., Ren, X., Wu, D., & Ding, K. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200976s · Cited by 71 · see citing works
Tremblay, A., Dufour, C. R., Ghahremani, M., Reudelhuber, T. L., & Giguère, V. (2009) · Molecular Endocrinology · doi:10.1210/me.2009-0254 · Cited by 68 · see citing works
Metabolism and autophagy in the immune system: immunometabolism comes of age
Rathmell, J. C. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01158.x · Cited by 68 · see citing works
Parkin degrades estrogen-related receptors to limit the expression of monoamine oxidases
Ren, Y., Jiang, H., Ma, D., Nakaso, K., & Feng, J. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq550 · Cited by 67 · see citing works
Mapping of INS promoter interactions reveals its role in long-range regulation of SYT8 transcription
Xu, Z., Wei, G., Chepelev, I., Zhao, K., & Felsenfeld, G. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1993 · Cited by 67 · see citing works
Perry, M.-C., Dufour, C. R., Tam, I. S., B'Chir, W., & Giguère, V. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1281 · Cited by 63 · see citing works
Auerbach, S. S., Filer, D. L., Reif, D. M., Walker, V. R., Holloway, A. C., Schlezinger, J. J., Srinivasan, S., Svoboda, D. L., Judson, R., Bucher, J. R., et al. (2016) · Environmental Health Perspectives · doi:10.1289/ehp.1510456 · Cited by 60 · see citing works
“…the interaction with ERRα has not been previously identified and is of interest given the apparent role of ERRs in regulating adipogenesis, energy homeostasis, diabetes, and heart disease (Bonnelye and Aubin 2013; Deblois and Giguère 2011; Ju et al. 2012; Ranhotra 2010; Villena and Kralli 2008).”
BackgroundLi, Y., He, L., Zeng, N., Sahu, D., Cadenas, E., Shearn, C., Li, W., & Stiles, B. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.450353 · Cited by 58 · see citing works
“ERR controls expressions of both nuclear and mitochondrial transcription factors involved inmitochondrial biogenesis (53).”
BackgroundStallcup, M. R., & Poulard, C. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.02.006 · Cited by 63 · see citing works
ERRs and cancers: Effects on metabolism and on proliferation and migration capacities
Bianco, S., Sailland, J., & Vanacker, J.-M. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.03.014 · Cited by 59 · see citing works
Jo, Y. S., Ryu, D., Maida, A., Wang, X., Evans, R. M., Schoonjans, K., & Auwerx, J. H. (2015) · Hepatology · doi:10.1002/hep.27907 · Cited by 58 · see citing works
Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration
Sailland, J., Tribollet, V., Forcet, C., Billon, C., Barenton, B., Carnesecchi, J., Bachmann, A., Gauthier, K. C., Yu, S., Giguère, V., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402094111 · Cited by 57 · see citing works
Nutrient Sensing via mTOR in T Cells Maintains a Tolerogenic Microenvironment
Howie, D., Waldmann, H., & Cobbold, S. P. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00409 · Cited by 57 · see citing works
Brown, E. L., Hazen, B. C., Eury, E., Wattez, J.-S., Gantner, M. L., Albert, V., Chau, S., Sánchez-Alavez, M., Conti, B., & Kralli, A. (2018) · iScience · doi:10.1016/j.isci.2018.03.005 · Cited by 55 · see citing works
“…agonism (e.g., mitochondrial function, oxidative phosphorylation, and TCA cycle) were known to be regulated by ERRs (Hock and Kralli, 2009; Villena and Kralli, 2008), our RNA sequencing data show a much broader set of adrenergic responses, extending beyond the control of mitochondrial…”
BackgroundSelf-citationAging, senescence and mitochondria: the PGC-1/ERR axis
Vernier, M., & Giguère, V. (2020) · Journal of Molecular Endocrinology · doi:10.1530/jme-20-0196 · Cited by 51 · see citing works
“2007, Villena & Kralli 2008, Hock & Kralli 2009, Deblois et al.”
BackgroundCholesterol as an Endogenous ERRα Agonist: A New Perspective to Cancer Treatment
Casaburi, I., Chimento, A., Luca, A. D., Nocito, M. C., Sculco, S., Avena, P., Trotta, F., Rago, V., Sirianni, R., & Pezzi, V. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00525 · Cited by 50 · see citing works
Estrogen-related receptors: novel potential regulators of osteoarthritis pathogenesis
Tang, J., Liu, T., Wen, X., Zhou, Z., Yan, J., Gao, J.-P., & Zuo, J. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00270-x · Cited by 50 · see citing works
Svensson, K., Albert, V., Cardel, B., Salatino, S., & Handschin, C. (2016) · The FASEB Journal · doi:10.1096/fj.201500128 · Cited by 49 · see citing works
Smith, S. S., Dole, N. S., Franceschetti, T., Hrdlicka, H. C., & Delany, A. M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.737890 · Cited by 49 · see citing works
“Although estrogen-related receptors have been linked to energy homeostasis and can display circadian regulation, it is not known whether these mechanisms are active in calvaria (54, 55).”
BackgroundAt the crossroad of T cells, adipose tissue, and diabetes
Matarese, G., Procaccini, C., & Rosa, V. D. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01154.x · Cited by 47 · see citing works
Li, Y., Birnbaumer, L., & Teng, C. T. (2010) · Molecular Endocrinology · doi:10.1210/me.2009-0148 · Cited by 47 · see citing works
Zhou, Q., Xu, H., Liang, Y., Liang, Y., Zhang, X., Tan, B., Yi, Q., Tian, J., & Zhu, J. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.12.006 · Cited by 46 · see citing works
Bisphenol A modulates the metabolic regulator oestrogen-related receptor-α in T-cells
Cipelli, R., Harries, L. W., Okuda, K., Yoshihara, S., Melzer, D. R., & Galloway, T. S. (2013) · Reproduction · doi:10.1530/rep-13-0423 · Cited by 46 · see citing works
ERR receptors as potential targets in osteoporosis
Gallet, M., & Vanacker, J.-M. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.06.008 · Cited by 46 · see citing works
Saul, M. C., Seward, C. H., Troy, J. M., Zhang, H., Sloofman, L. G., Lu, X., Weisner, P. A., Caetano-Anolles, D., Sun, H., Zhao, S. D., et al. (2017) · Genome Research · doi:10.1101/gr.214221.116 · Cited by 46 · see citing works
“At the nexus of these expression and regulatory dynamics stands the TF ESRRA, a nuclear receptor known as a key regulator of metabolism and differentiation (for review, see Villena and Kralli 2008).”
miR-135a Inhibits the Invasion of Cancer Cells via Suppression of ERRα
Tribollet, V., Barenton, B., Kroiss, A., Vincent, S., Zhang, L., Forcet, C., Cerutti, C., Perian, S., Allioli, N., Samarut, J., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156445 · Cited by 45 · see citing works
Senga, S., Kawaguchi, K., Kobayashi, N., Ando, A., & Fujii, H. (2018) · Oncotarget · doi:10.18632/oncotarget.25878 · Cited by 45 · see citing works
“ERRs are considered orphan nuclear receptors, because the endogenous ligands for ERRs have not yet been identified [62].”
Absence of ERRα in Female Mice Confers Resistance to Bone Loss Induced by Age or Estrogen-Deficiency
Teyssier, C., Gallet, M., Rabier, B., Monfoulet, L., Dine, J., Macari, C., Espallergues, J., Horard, B., Giguère, V., Cohen-Solal, M. E., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007942 · Cited by 44 · see citing works
Estrogen Mediates an Atherosclerotic-Protective Action via Estrogen Receptor Alpha/SREBP-1 Signaling
Xie, F., Li, X., Xu, Y., Cheng, D., Xia, X., Lv, X., Yuan, G., & Peng, C. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.895916 · Cited by 43 · see citing works
“E2 Influenced ESRα Expression ESRα is a nuclear hormone receptor that governs expression of the target genes involved in numerous metabolic pathways, including those guiding mitochondrial oxidative phosphorylation and lipid metabolism (25).”
BackgroundRossi, M., Colecchia, D., Iavarone, C., Strambi, A., Piccioni, F., Verrotti, A. C., & Chiariello, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.179523 · Cited by 43 · see citing works
SOCS1 is a negative regulator of metabolic reprogramming during sepsis
Piñeros, A. R., Glosson, N. L., Brandt, S. L., Wang, S., Wong, H. R., Sturgeon, S. M., McCarthy, B. P., Territo, P. R., Alves-Filho, J. C., & Serezani, C. H. (2017) · JCI Insight · doi:10.1172/jci.insight.92530 · Cited by 43 · see citing works
“The orphan nuclear receptor ERR-α is both a regulator of energy metabolism and a negative regulator of inflammation (77).”
BackgroundTranscriptional regulation of temperature-induced remodeling of muscle bioenergetics in goldfish
Bremer, K., Monk, C. T., Gurd, B. J., & Moyes, C. D. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00603.2011 · Cited by 42 · see citing works
“It works with PGC-1 / to regulate PGC-1 , NRF-1, NRF-2 , TR , and PPAR as well as itself (23, 55, 62, 64).”
The estrogen-related receptors: orphans orchestrating myriad functions
Ranhotra, H. S. (2012) · Journal of Receptors and Signal Transduction · doi:10.3109/10799893.2011.647350 · Cited by 41 · see citing works
“In adipocyte growth and differentiation The role of the ERRs in the various aspects of WAT and BAT metabolism is known to some extent and has been widely reviewed (2,3,5,52,53).”
BackgroundGuh, Y.-J., & Hwang, P. (2016) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2016.08.009 · Cited by 41 · see citing works
Emerging Roles of Orphan Nuclear Receptors in Cancer
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Involvement of estrogen receptor-related receptors in human ovarian endometriosis.
Cavallini, A., Resta, L., Caringella, A., Naro, E. D., Lippolis, C., & Loverro, G. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.04.032 · Cited by 34 · see citing works
Bonnelye, E., & Aubin, J. E. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1836 · Cited by 39 · see citing works
Kammerer, M., Gutzwiller, S., Stauffer, D., Delhon, I., Seltenmeyer, Y., & Fournier, B. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.01.024 · Cited by 38 · see citing works
ES1 is a mitochondrial enlarging factor contributing to form mega-mitochondria in zebrafish cones
Masuda, T., Wada, Y., & Kawamura, S. (2016) · Scientific Reports · doi:10.1038/srep22360 · Cited by 38 · see citing works
Complementary Roles of Estrogen-Related Receptors in Brown Adipocyte Thermogenic Function
Gantner, M. L., Hazen, B. C., Eury, E., Brown, E. L., & Kralli, A. (2016) · Endocrinology · doi:10.1210/en.2016-1767 · Cited by 38 · see citing works
Self-citation
- Authors
- Villena, J. A., & Kralli, A.
- Affiliations
- Vall d'Hebron Institut de Recerca (ES)
- Scripps Research Institute (US)
- ORCID
- Villena, Josep A.
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 19
- Issue
- 8
- Pages
- 269-276
- ISSN
- 1043-2760 (ISSN-L)
- PMC
- PMC2786240
- OpenAlex
- W2009727112
- Cited by
- 252
- References
- 68
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 16 · 2023: 9 · 2022: 12 · 2021: 12 · 2020: 12 · 2019: 13 · 2018: 14 · 2017: 18 · 2016: 20 · 2015: 19 · 2014: 15 · 2013: 15 · 2012: 21
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064951, DK 064951, DK074660, R21DK074660)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- estrogen-related receptor alpha, orphan nuclear receptor, energy metabolism, metabolic adaptation, cold exposure, cardiac overload, infection, metabolic disorders, transcriptional regulation
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, ERRalpha Estrogen-Related Receptor, Animals, Energy Metabolism, Multigene Family, Humans, Models, Biological, Receptors, Estrogen, Transcription Factors, Trans-Activators, Mice, Knockout, Mice, Metabolic Networks and Pathways
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