Regulation of PPARγCoactivator-1αFunction and Expression in Muscle: Effect of Exercise
Open accessAbstract
PPARγ coactivator-1α (PGC-1α) is considered to be a major regulator of mitochondrial biogenesis. Though first discovered in brown adipose tissue, this coactivator has emerged as a coordinator of mitochondrial biogenesis in skeletal muscle via enhanced transcription of many nuclear genes encoding mitochondrial proteins. Stimuli such as exercise provoke the activation of signalling cascades that lead to the induction of PGC-1α. Posttranslational modifications also regulate the function of PGC-1α, with a multitude of upstream molecules targeting the protein to modify its activity and/or expression. Previous research has established a positive correlation between resistance to fatigue and skeletal muscle mitochondrial content. Recently, studies have begun to elucidate the specific role of PGC-1α in exercise-related skeletal muscle adaptations, with several studies identifying it as a dominant regulator of organelle synthesis. This paper will highlight the function, regulation, and expression of PGC-1α, as well as the role of the coactivator during exercise adaptations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The insulin sensitising effect of exercise is paralleled by a concomitant exercise-induced upregulation of PGC1α.
“In support of this notion, the insulin sensitising effect of exercise (Meex et al., 2010) is paralleled by a concomitant exercise-induced upregulation of PGC 1α (Uguccioni et al., 2010).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Uguccioni et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Wu, 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
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
A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864 · see citing works
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · see citing works
Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160 · see citing works
Transcriptional 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
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491 · see citing works
Puigserver, P., & Spiegelman, B. M. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0012 · Cited by 2,076 · see citing works
PGC-1α: a key regulator of energy metabolism
Liang, H., & Ward, W. F. (2006) · AJP Advances in Physiology Education · doi:10.1152/advan.00052.2006 · Cited by 1,250 · see citing works
AMPK and PPARδ Agonists Are Exercise Mimetics
Narkar, V. A., Downes, M., Yu, R. T., Embler, E., Wang, Y.-X., Banayo, E., Mihaylova, M. M., Nelson, M. C., Zou, Y., Juguilon, H., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.051 · Cited by 1,222 · see citing works
Vega, R. B., Huss, J. M., & Kelly, D. P. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.5.1868-1876.2000 · Cited by 1,195 · see citing works
Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice
Lin, J., Wu, P.-H., Tarr, P. T., Lindenberg, K. S., St-Pierre, J., Zhang, C.-Y., Mootha, V. K., Jäger, S., Vianna, C. R., Reznick, R. M., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.013 · Cited by 1,162 · see citing works
Regulation of Muscle Fiber Type and Running Endurance by PPARδ
Wang, Y.-X., Zhang, C.-L., Yu, R. T., Cho, H. K., Nelson, M. C., Bayuga-Ocampo, C. R., Ham, J., Kang, H., & Evans, R. M. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020294 · Cited by 1,089 · see citing works
SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α
Nemoto, S., Fergusson, M. M., & Finkel, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501485200 · Cited by 1,047 · see citing works
Zong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., & Shulman, G. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252625599 · Cited by 1,036 · 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
Exercise induces transient transcriptional activation of the PGC‐1α gene in human skeletal muscle
Pilegaard, H., Saltin, B., & Neufer, P. D. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.034850 · Cited by 885 · see citing works
Cytokine Stimulation of Energy Expenditure through p38 MAP Kinase Activation of PPARγ Coactivator-1
Puigserver, P., Rhee, J., Lin, J., Wu, Z., Yoon, J. C., Zhang, C.-Y., Krauss, S., Mootha, V. K., Lowell, B. B., & Spiegelman, B. M. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00390-2 · Cited by 732 · cited 1× · see citing works
“In skeletal muscle, PGC1α expression tends to coincide with signalling pathways typically activated with mitochondrial biogenesis, such as those induced by endurance exercise.”
BackgroundHandschin, 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
Akimoto, T., Pohnert, S. C., Li, P., Zhang, M., Gumbs, C., Rosenberg, P. B., Williams, R. S., & Yan, Z. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408862200 · Cited by 714 · see citing works
Gleyzer, N., Vercauteren, K., & Scarpulla, R. C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.4.1354-1366.2005 · Cited by 711 · see citing works
DNA replication and transcription in mammalian mitochondria.
Falkenberg, M., Larsson, N., & Gustafsson, C. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060305.152028 · Cited by 686 · 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
Schreiber, S., Emter, R., Hock, M. B., Knutti, D., Cardenas, J., Podvinec, M., Oakeley, E. J., & Kralli, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308686101 · Cited by 657 · 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
Activation of PPARγ Coactivator-1 Through Transcription Factor Docking
Puigserver, P., Adelmant, G., Wu, Z., Fan, M., Xu, J., O’Malley, B. W., & Spiegelman, B. M. (1999) · Science · doi:10.1126/science.286.5443.1368 · Cited by 596 · see citing works
Lin, J., Puigserver, P., Donovan, J., Tarr, P., & Spiegelman, B. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c100631200 · Cited by 552 · see citing works
St‐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
Nuclear 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
Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1α transcription coactivator
Li, X., Monks, B., Ge, Q., & Birnbaum, M. J. (2007) · Nature · doi:10.1038/nature05861 · Cited by 487 · see citing works
Lerin, C., Rodgers, J. T., Kalume, D. E., Kim, S.-H., Pandey, A., & Puigserver, P. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.013 · Cited by 443 · see citing works
Direct Coupling of Transcription and mRNA Processing through the Thermogenic Coactivator PGC-1
Monsalve, M., Wu, Z., Adelmant, G., Puigserver, P., Fan, M., & Spiegelman, B. M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00031-9 · Cited by 395 · 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
Coordination of metabolic plasticity in skeletal muscle
Hood, D. A., Irrcher, I., Ljubicic, V., & Joseph, A.-M. (2006) · Journal of Experimental Biology · doi:10.1242/jeb.02182 · Cited by 370 · see citing works
Self-citationIrrcher, I., Ljubicic, V., & Hood, D. A. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00267.2007 · Cited by 356 · see citing works
Self-citationIrrcher, I., Adhihetty, P. J., Sheehan, T. E., Joseph, A.-M., & Hood, D. A. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00409.2002 · Cited by 315 · see citing works
Self-citationFan, M., Rhee, J., St-Pierre, J., Handschin, C., Puigserver, P., Lin, J., Jäeger, S., Erdjument-Bromage, H., Tempst, P., & Spiegelman, B. M. (2004) · Genes & Development · doi:10.1101/gad.1152204 · Cited by 309 · see citing works
Corepressors selectively control the transcriptional activity of PPARγ in adipocytesPreprint
Guan, H.-P., Ishizuka, T., Chui, P. C., Lehrke, M., & Lazar, M. A. (2005) · Genes & Development · doi:10.1101/gad.1263305 · Cited by 293 · see citing works
A Tissue-Specific Coactivator of Steroid Receptors, Identified in a Functional Genetic Screen
Knutti, D., Kaul, A., & Kralli, A. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.7.2411-2422.2000 · Cited by 286 · see citing works
Effects of α‐AMPK knockout on exercise‐induced gene activation in mouse skeletal muscle
Jørgensen, S. B., Wojtaszewski, J. F. P., Viollet, B., Andreelli, F., Birk, J. B., Hellsten, Y., Schjerling, P., Vaulont, S., Neufer, P. D., Richter, E. A., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-3144fje · Cited by 274 · see citing works
Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor
Knutti, D., Kressler, D., & Kralli, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171184698 · Cited by 271 · see citing works
Geng, T., Li, P., Okutsu, M., Yin, X., Kwek, J., Zhang, M., & Yan, Z. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00481.2009 · Cited by 263 · see citing works
Raising Ca2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle
Ojuka, E., Jones, T. E., Han, D.-H., Chen, M. M., & Holloszy, J. (2003) · The FASEB Journal · doi:10.1096/fj.02-0951com · Cited by 258 · see citing works
cDNA Cloning and mRNA Analysis of PGC-1 in Epitrochlearis Muscle in Swimming-Exercised Rats
Goto, M., Terada, S., Kato, M., Katoh, M., Yokozeki, T., Tabata, I., & Shimokawa, T. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3134 · Cited by 258 · 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 · cited 1× · see citing works
“Gain-of-function experiments resulted in increased muscle glucose uptake and decreased rates of glycolysis, along with concomitant increases in muscle glycogen stores and the prevention of glycogen depletion in response to exercise [52].”
BackgroundPGC-1β in the Regulation of Hepatic Glucose and Energy Metabolism
Lin, J., Tarr, P. T., Yang, R., Rhee, J., Puigserver, P., Newgard, C. B., & Spiegelman, B. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303643200 · Cited by 242 · cited 1× · see citing works
“…Editor: Josep Bassaganya-Riera Copyright © 2010 Giulia Uguccioni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.”
MethodThe PGC-1-related Protein PERC Is a Selective Coactivator of Estrogen Receptor α
Kressler, D., Schreiber, S., Knutti, D., & Kralli, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201134200 · Cited by 239 · see citing works
Leick, L., Wojtaszewski, J. F. P., Johansen, S. T., Kiilerich, K., Comes, G., Hellsten, Y., Hidalgo, J., & Pilegaard, H. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00666.2007 · Cited by 236 · see citing works
Amat, R., Planavila, A., Chen, S. L., Iglesias, R., Giralt, M., & Villarroya, F. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.022749 · Cited by 218 · see citing works
AMP-Activated Protein Kinase-Regulated Activation of the PGC-1α Promoter in Skeletal Muscle Cells
Irrcher, I., Ljubicic, V., Kirwan, A. F., & Hood, D. A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003614 · Cited by 211 · see citing works
Self-citationEsterbauer, H., Oberkofler, H., Krempler, F., & Patsch, W. (1999) · Genomics · doi:10.1006/geno.1999.5977 · Cited by 201 · see citing works
The role of PGC-1α on mitochondrial function and apoptotic susceptibility in muscle
Adhihetty, P. J., Uguccioni, G., Leick, L., Hidalgo, J., Pilegaard, H., & Hood, D. A. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00070.2009 · Cited by 168 · see citing works
Self-citationLjubicic, 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
Self-citationPogozelski, A. R., Geng, T., Li, P., Yin, X., Lira, V. A., Zhang, M., Chi, J.-T., & Yan, Z. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007934 · Cited by 164 · see citing works
Gordon, J. W., Rungi, A. A., Inagaki, H., & Hood, D. A. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.90.1.389 · Cited by 160 · see citing works
Self-citationSUMOrganization of the nucleus
Heun, P. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.04.014 · Cited by 144 · see citing works
Vercauteren, K., Pasko, R. A., Gleyzer, N., Marino, V. M., & Scarpulla, R. C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00585-06 · Cited by 109 · see citing works
SUMOylation Attenuates the Function of PGC-1α
Rytinki, M. M., & Palvimo, J. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.038943 · Cited by 108 · see citing works
Vercauteren, K., Gleyzer, N., & Scarpulla, R. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710150200 · Cited by 83 · see citing works
Concentration dependence of the dielectric constant in mixed oxides MxOyMp′Oq
Devine, R. A. B., & Revesz, A. G. (2001) · Journal of Applied Physics · doi:10.1063/1.1375806 · Cited by 76 · see citing works
Connor, M. K., Irrcher, I., & Hood, D. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100272200 · Cited by 71 · see citing works
Self-citationVercauteren, K., Gleyzer, N., & Scarpulla, R. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806434200 · Cited by 70 · see citing works
Transcriptional Control of the Pgc-1α Gene in Skeletal Muscle In Vivo
Yan, Z., Li, P., & Akimoto, T. (2007) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e3180a03169 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sergi, D., Naumovski, N., Heilbronn, L. K., Abeywardena, M., O’Callaghan, N., Lionetti, L., & Luscombe-Marsh, N. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00532 · Cited by 347 · see citing works
“In support of this notion, the insulin sensitising effect of exercise (Meex et al., 2010) is paralleled by a concomitant exercise-induced upregulation of PGC 1α (Uguccioni et al., 2010).”
BackgroundVaughan, 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
- Authors
- Uguccioni, G., D'souza, D., & Hood, D. A.
- Affiliations
- York University (CA)
- School of Kinesiology and Health Science, York University, Toronto, ON, Canada M3J 1P3
- Corresponding author
- Hood, David A.
- ORCID
- Hood, David A.
- Venue
- PPAR Research
- Publisher
- Wiley
- Published
- 2010
- Volume
- 2010
- Pages
- 1-7
- ISSN
- 1687-4757 (ISSN-L)
- 1687-4765
- PMC
- PMC2933917
- OpenAlex
- W2105555168
- Cited by
- 28
- References
- 64
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 5 · 2012: 2
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PPAR Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- 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, physical activity, skeletal muscle, mitochondrial biogenesis, post-translational modification, exercise adaptation, fatigue resistance, mitochondrial content
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
