ERRα and Gabpa/b specify PGC-1α-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle.
Open accessAbstract
Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression in skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be mediated by the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). By combining PGC-1alpha-induced genome-wide transcriptional profiles with a computational strategy to detect cis-regulatory motifs, we identified estrogen-related receptor alpha (Erralpha) and GA repeat-binding protein alpha as key transcription factors regulating the OXPHOS pathway. Interestingly, the genes encoding these two transcription factors are themselves PGC-1alpha-inducible and contain variants of both motifs near their promoters. Cellular assays confirmed that Erralpha and GA-binding protein a partner with PGC-1alpha in muscle to form a double-positive-feedback loop that drives the expression of many OXPHOS genes. By using a synthetic inhibitor of Erralpha, we demonstrated its key role in PGC-1alpha-mediated effects on gene regulation and cellular respiration. These results illustrate the dissection of gene regulatory networks in a complex mammalian system, elucidate the mechanism of PGC-1alpha action in the OXPHOS pathway, and suggest that Erralpha agonists may ameliorate insulin-resistance in individuals with type 2 diabetes mellitus.
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PGC1α is a master regulator of mitochondrial biogenesis and OXPHOS gene expression.
“Puigserver and Spiegelman (5) demonstrated that PGC1␣ is a master regulator of mitochondrial biogenesis and OXPHOS gene expression (33).”
From A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle (2005) · cites this paper as [33]
PGC-1 family members interact with ERRs to transactivate transcription of oxidative genes and mitofusins.
“PGC-1 family members interact with the family of estrogen-related nuclear receptors, or ERRs, to transactivate transcription of oxidative genes (275) and mitofusins (276).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [275]
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Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Self-citationWu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139 · see citing works
Self-citationTranscriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546 · see citing works
Self-citationSystematic determination of genetic network architecture
Tavazoie, S., Hughes, J. D., Campbell, M. J., Cho, R. J., & Church, G. M. (1999) · Nature Genetics · doi:10.1038/10343 · Cited by 2,509 · see citing works
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321 · see citing works
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107 · see citing works
Puigserver, P., & Spiegelman, B. M. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0012 · Cited by 2,076 · see citing works
Self-citationPatti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952 · see citing works
Sequencing and comparison of yeast species to identify genes and regulatory elements
Kellis, M., Patterson, N. J., Endrizzi, M. G., Birren, B. W., & Lander, E. S. (2003) · Nature · doi:10.1038/nature01644 · Cited by 1,731 · see citing works
Self-citationA genomic regulatory network for development
Davidson, E. H., Rast, J. P., Oliveri, P., Ransick, A., Calestani, C., Yuh, C.-H., Minokawa, T., Amore, G., Hinman, V., Arenas-Mena, C., et al. (2002) · Science · doi:10.1126/science.1069883 · Cited by 1,567 · see citing works
Human–Mouse Alignments with BLASTZPreprint
Schwartz, S., Kent, W. J., Smit, A., Zhang, Z., Baertsch, R., Hardison, R. C., Haussler, D. H., & Miller, W. (2002) · Genome Research · doi:10.1101/gr.809403 · Cited by 1,231 · see citing works
Mootha, V. K., Bunkenborg, J., Olsen, J. V., Hjerrild, M., Wisniewski, J. R., Stahl, E., Bolouri, M. S., Ray, H. N., Sihag, S., Kamal, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00926-7 · Cited by 889 · see citing works
Self-citationVirbasius, J. V., & Scarpulla, R. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.4.1309 · Cited by 819 · see citing works
Handschin, C., Rhee, J., Lin, J., Tarr, P. T., & Spiegelman, B. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1232352100 · Cited by 729 · see citing works
Self-citationRegulatory element detection using correlation with expression
Bussemaker, H. J., Li, H., & Siggia, E. D. (2001) · Nature Genetics · doi:10.1038/84792 · Cited by 721 · see citing works
Liu, X. S., Brutlag, D. L., & Liu, J. S. (2002) · Nature Biotechnology · doi:10.1038/nbt717 · Cited by 670 · see citing works
Michael, L. F., Wu, Z., Cheatham, R. B., Puigserver, P., Adelmant, G., Lehman, J. J., Kelly, D. P., & Spiegelman, B. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061035098 · Cited by 663 · see citing works
Self-citationSt‐Pierre, J., Lin, J. D., Krauss, S., Tarr, P. T., Yang, R., Newgard, C. B., & Spiegelman, B. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301850200 · Cited by 543 · see citing works
Self-citationHuss, J. M., Kopp, R. P., & Kelly, D. P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206324200 · Cited by 480 · see citing works
Schreiber, S., Knutti, D., Brogli, K., Uhlmann, T., & Kralli, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212923200 · Cited by 458 · see citing works
SLADEK, R. M., Bader, J.-A., & Giguère, V. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5400 · Cited by 375 · see citing works
Scarpulla, R. (2002) · Gene · doi:10.1016/s0378-1119(01)00809-5 · Cited by 371 · see citing works
Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor α.
Luo, J., Sladek, R., Carrier, J., Bader, J.-A., Richard, D., & Giguère, V. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.7947-7956.2003 · Cited by 370 · see citing works
Kamei, Y., Ohizumi, H., Fujitani, Y., Nemoto, T., Tanaka, T., Takahashi, N., Kawada, T., Miyoshi, M., Ezaki, O., & Kakizuka, A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2135217100 · Cited by 357 · see citing works
Integrating regulatory motif discovery and genome-wide expression analysis
Conlon, E. M., Liu, X. S., Lieb, J. D., & Liu, J. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0630591100 · Cited by 343 · see citing works
The Structure of GABPα/β: An ETS Domain- Ankyrin Repeat Heterodimer Bound to DNA
Batchelor, A. H., Piper, D. E., de la Brousse, F. C., McKnight, S. L., & Wolberger, C. (1998) · Science · doi:10.1126/science.279.5353.1037 · Cited by 291 · see citing works
Schadt, E. E., Cheng, L., Ellis, B., & Wong, W. H. (2001) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10073 · Cited by 288 · see citing works
Gene Expression Profile in Skeletal Muscle of Type 2 Diabetes and the Effect of Insulin Treatment
Sreekumar, R., Halvatsiotis, P., Schimke, J. C., & Nair, K. S. (2002) · Diabetes · doi:10.2337/diabetes.51.6.1913 · Cited by 257 · see citing works
Johnston, S. D., Liu, X., Zuo, F., Eisenbraun, T. L., Wiley, S. R., Kraus, R. J., & Mertz, J. E. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.3.9897 · Cited by 170 · see citing works
Mechanisms of transactivation by retinoic acid receptors
Stunnenberg, H. G. (1993) · BioEssays · doi:10.1002/bies.950150504 · Cited by 155 · see citing works
Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity
Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E., Han, D.-H., Nolte, L. A., Ojuka, E. O., Chen, M. W., & Holloszy, J. O. (2003) · The FASEB Journal · doi:10.1096/fj.03-0049com · Cited by 106 · see citing works
Qiu, P. S. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.08.052 · Cited by 105 · see citing works
Zhong, S. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg598 · Cited by 91 · see citing works
The α and β Subunits of the GA-binding Protein Form a Stable Heterodimer in Solution
Chinenov, Y. V., Henzl, M. T., & Martin, M. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.11.7749 · Cited by 51 · see citing works
Chinenov, Y. V., Coombs, C., & Martin, M. E. (2000) · Gene · doi:10.1016/s0378-1119(00)00500-x · Cited by 18 · see citing works
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Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Self-citationWallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · see citing works
DeFronzo, R. A. (2009) · Diabetes · doi:10.2337/db09-9028 · Cited by 3,016 · see citing works
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233 · see citing works
Self-citationButyrate improves insulin sensitivity and increases energy expenditure in mice
Gao, Z., Yin, J., Zhang, J., Ward, R. E., Martin, R. J., Lefevre, M., Cefalu, W. T., & Ye, J. (2009) · Diabetes · doi:10.2337/db08-1637 · Cited by 2,204 · see citing works
Metabolic control through the PGC-1 family of transcription coactivators
Lin, J., Handschin, C., & Spiegelman, B. M. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.004 · Cited by 2,130 · see citing works
“…this includes NRF-1 and NRF-2 (Wu et al., 1999) and the nuclear hormone receptors, such as PPARα (Vega et al., 2000), PPARδ (Wang et al., 2003), ERRα (Huss et al., 2002; Huss et al., 2004; Kamei et al., 2003; Mootha et al., 2004; Schreiber et al., 2004), and TR (Zhang et al., 2004b) (Table 1).”
BackgroundSelf-citationActivation of a metabolic gene regulatory network downstream of mTOR complex 1
Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020 · see citing works
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology
Pagliarini, D. J., Calvo, S. E., Chang, B., Sheth, S. A., Vafai, S. B., Ong, S.-E., Walford, G. A., Sugiana, C., Boneh, A., Chen, W. K., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.016 · Cited by 1,994 · see citing works
Self-citationXie, X., Lu, J., Kulbokas, E. J., Golub, T. R., Mootha, V., Lindblad-Toh, K., Lander, E. S., & Kellis, M. (2005) · Nature · doi:10.1038/nature03441 · Cited by 1,872 · see citing works
Self-citationTranscriptional paradigms in mammalian mitochondrial biogenesis and function
Scarpulla, R. C. (2008) · Physiological Reviews · doi:10.1152/physrev.00025.2007 · Cited by 1,666 · see citing works
PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure
Cantó, C., & Auwerx, J. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328328d0a4 · Cited by 1,624 · see citing works
mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex
Cunningham, J. T., Rodgers, J. T., Arlow, D. H., Vazquez, F., Mootha, V. K., & Puigserver, P. (2007) · Nature · doi:10.1038/nature06322 · Cited by 1,488 · see citing works
Self-citationExercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway
Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., Lin, J. D., Greenberg, M. E., & Spiegelman, B. M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.008 · Cited by 1,440 · see citing works
Self-citationMitoCarta2.0: an updated inventory of mammalian mitochondrial proteins
Calvo, S. E., Clauser, K. R., & Mootha, V. K. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1003 · Cited by 1,251 · see citing works
Self-citationPathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342 · see citing works
Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC‐1α
Gerhart‐Hines, Z., Rodgers, J. T., Bare, O., Lerin, C., Kim, S., Mostoslavsky, R., Alt, F. W., Wu, Z., & Puigserver, P. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601633 · Cited by 1,294 · see citing works
Self-citationMetabolic 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
Microglial brain region-dependent diversity and selective regional sensitivities to aging
Grabert, K., Michoel, T., Karavolos, M. H., Clohisey, S., Baillie, J. K., Stevens, M. P., Freeman, T. C., Summers, K. M., & McColl, B. W. (2016) · Nature Neuroscience · doi:10.1038/nn.4222 · Cited by 1,151 · see citing works
Handschin, C., & Spiegelman, B. M. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0037 · Cited by 1,090 · see citing works
Self-citationThe role of exercise and PGC1α in inflammation and chronic disease
Handschin, C., & Spiegelman, B. M. (2008) · Nature · doi:10.1038/nature07206 · Cited by 1,083 · see citing works
Self-citationHIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α
Arany, Z., Foo, S.-Y., Ma, Y., Ruas, J. L., Bommi-Reddy, A., Girnun, G., Cooper, M., Laznik, D., Chinsomboon, J., Rangwala, S. M., et al. (2008) · Nature · doi:10.1038/nature06613 · Cited by 1,054 · see citing works
Self-citationSandri, M., Lin, J., Handschin, C., Yang, W., Arany, Z. P., Lecker, S. H., Goldberg, A. L., & Spiegelman, B. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607795103 · Cited by 974 · see citing works
Self-citationAdiponectin and AdipoR1 Regulate PGC-1α and Mitochondria by Ca2+ and AMPK/SIRT1
Iwabu, M., Yamauchi, T., Okada-Iwabu, M., Sato, K., Nakagawa, T., Funata, M., Yamaguchi, M., Namiki, S., Nakayama, R., Tabata, M., et al. (2010) · Nature · doi:10.1038/nature08991 · Cited by 971 · see citing works
Leone, T. C., Lehman, J. J., Finck, B. N., Schaeffer, P. J., Wende, A. R., Boudina, S., Courtois, M., Wozniak, D. F., Sambandam, N., Bernal-Mizrachi, C., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030101 · Cited by 951 · see citing works
Transcriptional integration of mitochondrial biogenesis
Scarpulla, R. C., Vega, R. B., & Kelly, D. P. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.06.006 · Cited by 798 · see citing works
A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity
Okada-Iwabu, M., Yamauchi, T., Iwabu, M., Honma, T., Hamagami, K.-I., Matsuda, K., Yamaguchi, M., Tanabe, H., Kimura-Someya, T., Shirouzu, M., et al. (2013) · Nature · doi:10.1038/nature12656 · Cited by 757 · see citing works
Vazquez, F., Lim, J.-H., Chim, H., Bhalla, K., Girnun, G., Pierce, K., Clish, C. B., Granter, S. R., Widlund, H. R., Spiegelman, B. M., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2012.11.020 · Cited by 715 · see citing works
Self-citationKong, X., Wang, R., Xue, Y., Liu, X., Zhang, H., Chen, Y., Fang, F., & Chang, Y. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011707 · Cited by 718 · see citing works
Arany, Z., He, H., Lin, J., Hoyer, K., Handschin, C., Toka, O., Ahmad, F., Matsui, T., Chin, S., Wu, P.-H., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.03.002 · Cited by 694 · see citing works
Self-citationSparks, L. M., Xie, H., Koza, R. A., Mynatt, R., Hulver, M. W., Bray, G. A., & Smith, S. R. (2005) · Diabetes · doi:10.2337/diabetes.54.7.1926 · Cited by 629 · see citing works
Handschin, C., Chin, S., Li, P., Liu, F., Maratos-Flier, E., LeBrasseur, N. K., Yan, Z., & Spiegelman, B. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704817200 · Cited by 611 · see citing works
Self-citationThe Mitochondrial Proteome and Human Disease
Calvo, S. E., & Mootha, V. K. (2010) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082509-141720 · Cited by 590 · see citing works
Self-citationThe role of mitochondria in the pathogenesis of type 2 diabetes
Patti, M.-E., & Corvera, S. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0027 · Cited by 551 · see citing works
New insights into the role of mitochondria in aging: mitochondrial dynamics and more
Seo, A. Y., Joseph, A.-M., Dutta, D., Hwang, J. C. Y., Aris, J. P., & Leeuwenburgh, C. (2010) · Journal of Cell Science · doi:10.1242/jcs.070490 · Cited by 522 · see citing works
Segrè, A. V., DIAGRAM Consortium, MAGIC investigators, Groop, L., Mootha, V. K., Daly, M. J., & Altshuler, D. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001058 · Cited by 463 · see citing works
Self-citationNuclear control of respiratory gene expression in mammalian cells
Scarpulla, R. C. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20743 · Cited by 489 · see citing works
Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression.
Wright, D. C., Han, D.-H., Garcia-Roves, P. M., Geiger, P. C., Jones, T. E., & Holloszy, J. O. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m606116200 · Cited by 488 · see citing works
Jing, E., Emanuelli, B., Hirschey, M. D., Boucher, J., Lee, K. Y., Lombard, D., Verdin, E. M., & Kahn, C. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111308108 · Cited by 469 · see citing works
Pioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo
Bogacka, I., Xie, H., Bray, G. A., & Smith, S. R. (2005) · Diabetes · doi:10.2337/diabetes.54.5.1392 · Cited by 467 · see citing works
Koves, T. R., Li, P., An, J., Akimoto, T., Slentz, D., Ilkayeva, O., Dohm, G. L., Yan, Z., Newgard, C. B., & Muoio, D. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507621200 · Cited by 464 · see citing works
Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise
Schnyder, S., & Handschin, C. (2015) · Bone · doi:10.1016/j.bone.2015.02.008 · Cited by 419 · see citing works
Self-citationPGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity
Lira, V. A., Benton, C. R., Yan, Z., & Bonen, A. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00755.2009 · Cited by 412 · see citing works
Mitofusins 1/2 and ERRα expression are increased in human skeletal muscle after physical exercise
Cartoni, R., Léger, B., Hock, M. B., Praz, M., Crettenand, A., Pich, S., Ziltener, J., Luthi, F., Dériaz, O., Zorzano, A., et al. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.092031 · Cited by 406 · see citing works
Calvo, J. A., Daniels, T. G., Wang, X., Paul, A., Lin, J., Spiegelman, B. M., Stevenson, S. C., & Rangwala, S. M. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01231.2007 · Cited by 377 · see citing works
Self-citationLow-Volume Interval Training Improves Muscle Oxidative Capacity in Sedentary Adults
HOOD, M. S., LITTLE, J. P., TARNOPOLSKY, M. A., MYSLIK, F., & GIBALA, M. J. (2011) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3182199834 · Cited by 375 · see citing works
Egan, B., Carson, B. P., Garcia-Roves, P. M., Chibalin, A. V., Sarsfield, F. M., Barron, N., McCaffrey, N., Moyna, N. M., Zierath, J. R., & O’Gorman, D. J. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.188011 · Cited by 373 · see citing works
Arany, Z., Lebrasseur, N., Morris, C., Smith, E., Yang, W., Ma, Y., Chin, S., & Spiegelman, B. M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2006.12.003 · Cited by 370 · see citing works
Self-citationWende, A. R., Huss, J. M., Schaeffer, P. J., Giguère, V., & Kelly, D. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10684-10694.2005 · Cited by 354 · see citing works
Obesity-related derangements in metabolic regulation
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Soriano, F. X., Liesa, M., Bach, D., Chan, D. C., Palacín, M., & Zorzano, A. (2006) · Diabetes · doi:10.2337/db05-0509 · Cited by 343 · see citing works
Handschin, C., Choi, C. S., Chin, S., Kim, S., Kawamori, D., Kurpad, A. J., Neubauer, N., Hu, J., Mootha, V. K., Kim, Y.-B., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31785 · Cited by 335 · see citing works
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Wenz, T., Diaz, F., Spiegelman, B. M., & Moraes, C. T. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.07.006 · Cited by 297 · see citing works
Self-citationRetractedWu, Z., Huang, X., Feng, Y., Handschin, C., Feng, Y., Gullicksen, P. S., Bare, O., Labow, M., Spiegelman, B., & Stevenson, S. C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606714103 · Cited by 291 · see citing works
Self-citationEgan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
A role for the transcriptional coactivator PGC-1α in muscle refueling.
Wende, A. R., Schaeffer, P. J., Parker, G. J., Zechner, C., Han, D.-H., Chen, M. M., Hancock, C. R., Lehman, J. J., Huss, J. M., McClain, D. A., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707006200 · Cited by 257 · see citing works
ERRα: a metabolic function for the oldest orphan
Villena, J. A., & Kralli, A. (2008) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2008.07.005 · Cited by 252 · see citing works
“Second, inhibition of ERRα activity by either siRNA or an ERRα inverse agonist impairs the ability of PGC-1α to induce expression of energy metabolism genes and enhance mitochondrial biogenesis and oxidative capacity [26,29].”
BackgroundInfluentialPowelka, A. M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26040 · Cited by 236 · see citing works
Role of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes
Zorzano, A., Liesa, M., & Palacín, M. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.02.004 · Cited by 209 · see citing works
The coordination of nuclear and mitochondrial communication during aging and calorie restriction
Finley, L. W. S., & Haigis, M. C. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2009.03.003 · Cited by 207 · see citing works
Hernández-Alvarez, M. I., Thabit, H., Burns, N., Shah, S., Brema, I., Hatunic, M., Finucane, F., Liesa, M., Chiellini, C., Naon, D., et al. (2010) · Diabetes Care · doi:10.2337/dc09-1305 · Cited by 189 · see citing works
Dahlman, I., Forsgren, M., Sjögren, A., Nordström, E. A., Kaaman, M., Näslund, E., Attersand, A., & Arner, P. (2006) · Diabetes · doi:10.2337/db05-1421 · Cited by 184 · see citing works
Hypomorphic mutation of PGC-1β causes mitochondrial dysfunction and liver insulin resistance.
Vianna, C. R., Huntgeburth, M., Coppari, R., Choi, C. S., Lin, J., Krauss, S., Barbatelli, G., Tzameli, I., Kim, Y.-B., Cinti, S., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.11.003 · Cited by 181 · see citing works
Self-citationRegulatory circuits controlling white versus brown adipocyte differentiation
Hansen, J. B., & Kristiansen, K. (2006) · Biochemical Journal · doi:10.1042/bj20060402 · Cited by 178 · see citing works
Ljubicic, V., Joseph, A.-M., Saleem, A., Uguccioni, G., Collu-Marchese, M., Lai, R. Y. J., Nguyen, L. M.-D., & Hood, D. A. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.07.031 · Cited by 167 · see citing works
Exercise Induces Tissue-Specific Adaptations to Enhance Cardiometabolic Health
Ashcroft, S. P., Stocks, B., Egan, B., & Zierath, J. R. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.008 · Cited by 149 · see citing works
Patch, 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
Perrone, C. E., Mattocks, D. A. L., Jarvis-Morar, M., Plummer, J. D., & Orentreich, N. (2010) · Metabolism · doi:10.1016/j.metabol.2009.10.023 · Cited by 136 · see citing works
Muoio, D. M., & Koves, T. R. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h07-083 · Cited by 129 · see citing works
Vaughan, R. A., Garcia-Smith, R., Bisoffi, M., Conn, C. A., & Trujillo, K. A. (2012) · Lipids in Health and Disease · doi:10.1186/1476-511x-11-142 · Cited by 112 · see citing works
Sczelecki, S., Besse-Patin, A., Abboud, A., Kleiner, S., Laznik-Bogoslavski, D., Wrann, C. D., Ruas, J. L., Haibe-Kains, B., & Estall, J. L. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00578.2013 · Cited by 108 · see citing works
Wang, P., Liu, J., Li, Y., Wu, S., Luo, J., Yang, H., Subbiah, R., Chatham, J., Zhelyabovska, O., & Yang, Q. (2010) · Circulation Research · doi:10.1161/circresaha.109.206185 · Cited by 110 · see citing works
Rodríguez-Cuenca, S., Monjo, M., Gianotti, M., Proenza, A. M., & Roca, P. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00175.2006 · Cited by 108 · see citing works
Misu, H., Takamura, T., Matsuzawa, N., Shimizu, A., Ota, T., Sakurai, M., Ando, H., Arai, K., Yamashita, T., Honda, M., et al. (2007) · Diabetologia · doi:10.1007/s00125-006-0489-8 · Cited by 102 · see citing works
Pérez-Schindler, J., Summermatter, S., Salatino, S., Zorzato, F., Beer, M., Balwierz, P. J., van Nimwegen, E., Feige, J. N., Auwerx, J., & Handschin, C. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00877-12 · Cited by 82 · see citing works
Timmons, J. A., Norrbom, J., Schéele, C., Thonberg, H., Wahlestedt, C., & Tesch, P. (2006) · Genomics · doi:10.1016/j.ygeno.2005.09.007 · Cited by 79 · see citing works
Enhancement of muscle mitochondrial function by growth hormone
Short, K. R., Moller, N., Bigelow, M. L., Coenen-Schimke, J., & Nair, K. S. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1814 · Cited by 80 · see citing works
LaBarge, S., McDonald, M., Smith‐Powell, L., Auwerx, J., & Huss, J. M. (2014) · The FASEB Journal · doi:10.1096/fj.13-229211 · Cited by 74 · see citing works
Roman, E. A. F. R., Reis, D., Romanatto, T., Maimoni, D., Ferreira, E. A., Santos, G. A., Torsoni, A. S., Velloso, L. A., & Torsoni, M. A. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.08.007 · Cited by 71 · see citing works
Li, 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
Vaughan, R. A., Garcia-Smith, R., Bisoffi, M., Conn, C. A., & Trujillo, K. A. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.04.009 · Cited by 58 · see citing works
Liu, D., Zhang, Z., & Teng, C. T. (2005) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01586 · Cited by 56 · see citing works
Skeletal muscle gene expression profiling in mitochondrial disorders
Crimi, M., Bordoni, A., Menozzi, G., Riva, L., Fortunate, F., Galbiati, S., Del Bo, R., Pozzoli, U., Bresolin, N., & Comi, G. P. (2005) · The FASEB Journal · doi:10.1096/fj.04-3045fje · Cited by 56 · see citing works
Mouse phenogenomics: the fast track to “systems metabolism
Argmann, C. A., Chambon, P., & Auwerx, J. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.11.002 · Cited by 51 · see citing works
Baresic, M., Salatino, S., Kupr, B., van Nimwegen, E., & Handschin, C. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.01710-13 · Cited by 40 · see citing works
Self-citationHirvonen, J., Rajalin, A.-M., Wohlfahrt, G., Adlercreutz, H., Wähälä, K., & Aarnisalo, P. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.11.001 · Cited by 35 · see citing works
Dietary bioactive compounds as modulators of mitochondrial function
Vásquez-Reyes, S., Velázquez-Villegas, L. A., Vargas-Castillo, A., Noriega, L. G., Torres, N., & Tovar, A. R. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108768 · Cited by 35 · see citing works
Vaughan, R. A., Mermier, C. M., Bisoffi, M., Trujillo, K. A., & Conn, C. A. (2014) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-013-0301-4 · Cited by 34 · see citing works
Recent Advance in the Design of Small Molecular Modulators of Estrogen-Related Receptors
Lu, X., Peng, L., Lv, M., & ding, K. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212801227113 · Cited by 28 · see citing works
Sun, J., Huang, T., Qi, Z., You, S., Dong, J., Zhang, C., Qin, L., Zhou, Y., & Ding, S. (2017) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0043-104634 · Cited by 12 · see citing works
- Authors
- Mootha, V. K., Handschin, C., Arlow, D., Xie, X., St. Pierre, J., Sihag, S., Yang, W., Altshuler, D., Puigserver, P., Patterson, N., Willy, P. J., Schulman, I. G., Heyman, R. A., Lander, E. S., & Spiegelman, B. M.
- Affiliations
- Broad Institute (US)
- The Eli and Edythe L. Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and Dana–Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; and X-Ceptor Therapeutics Inc., San Diego, CA 92121
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-04-20
- Volume
- 101
- Issue
- 17
- Pages
- 6570-6575
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC404086
- OpenAlex
- W2131492087
- Cited by
- 688
- References
- 35
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 18 · 2023: 22 · 2022: 15 · 2021: 23 · 2020: 25 · 2019: 20 · 2018: 14 · 2017: 30 · 2016: 24 · 2015: 32 · 2014: 30 · 2013: 34 · 2012: 52
- FWCI
- 27.59
- Type
- journal article
- Language
- en
- Update notices
- correction (2005-07-08)
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Howard Hughes Medical Institute
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Schweizerische Akademie der Medizinischen Wissenschaften
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PGC-1α, estrogen-related receptor alpha, GABPA, oxidative phosphorylation, skeletal muscle, type 2 diabetes, insulin resistance, transcriptional coactivator, cis-regulatory motifs, positive feedback loop, gene regulatory networks, cellular respiration
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, ERRalpha Estrogen-Related Receptor, Animals, Base Sequence, Diabetes Mellitus, Experimental, DNA-Binding Proteins, Gene Expression Regulation, Oxidative Phosphorylation, Receptors, Estrogen, Transcription Factors, Transcription, Genetic, Transfection, Trans-Activators, Polymerase Chain Reaction, DNA Primers, Receptors, Cytoplasmic and Nuclear, Evolution, Molecular, GA-Binding Protein Transcription Factor, Mice
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