|
|
||||||||
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
1Correspondence: Washington University School of Medicine, Department of Medicine, Campus Box 8113, 4566 Scott Ave., St. Louis, MO 63110, USA. E-mail: jhollosz{at}im.wustl.edu
Endurance exercise induces increases in mitochondria and the GLUT4 isoform of the glucose transporter in muscle. Although little is known about the mechanisms underlying these adaptations, new information has accumulated regarding how mitochondrial biogenesis and GLUT4 expression are regulated. This includes the findings that the transcriptional coactivator PGC-1 promotes mitochondrial biogenesis and that NRF-1 and NRF-2 act as transcriptional activators of genes encoding mitochondrial enzymes. We tested the hypothesis that increases in PGC-1, NRF-1, and NRF-2 are involved in the initial adaptive response of muscle to exercise. Five daily bouts of swimming induced increases in mitochondrial enzymes and GLUT4 in skeletal muscle in rats. One exercise bout resulted in
twofold increases in full-length muscle PGC-1 mRNA and PGC-1 protein, which were evident 18 h after exercise. A smaller form of PGC-1 increased after exercise. The exercise induced increases in muscle NRF-1 and NRF-2 that were evident 12 to 18 h after one exercise bout. These findings suggest that increases in PGC-1, NRF-1, and NRF-2 represent key regulatory components of the stimulation of mitochondrial biogenesis by exercise and that PGC-1 mediates the coordinated increases in GLUT4 and mitochondria.Baar, K., Wende, A. R., Jones, T. E., Marison, M., Nolte, L. A., Chen, M., Kelly, D. P., Holloszy, J. O. Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1.
Key Words: GLUT4 mitochondrial biogenesis NRF-1 NRF-2
This article has been cited by other articles:
![]() |
M. F. N. O'Leary and D. A. Hood Effect of prior chronic contractile activity on mitochondrial function and apoptotic protein expression in denervated muscle J Appl Physiol, July 1, 2008; 105(1): 114 - 120. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Akimoto, P. Li, and Z. Yan Functional interaction of regulatory factors with the Pgc-1{alpha} promoter in response to exercise by in vivo imaging Am J Physiol Cell Physiol, July 1, 2008; 295(1): C288 - C292. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Pearen, S. A. Myers, S. Raichur, J. G. Ryall, G. S. Lynch, and G. E. O. Muscat The Orphan Nuclear Receptor, NOR-1, a Target of {beta}-Adrenergic Signaling, Regulates Gene Expression that Controls Oxidative Metabolism in Skeletal Muscle Endocrinology, June 1, 2008; 149(6): 2853 - 2865. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. R. LeMoine, C. E. Genge, and C. D. Moyes Role of the PGC-1 family in the metabolic adaptation of goldfish to diet and temperature J. Exp. Biol., May 1, 2008; 211(9): 1448 - 1455. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Calvo, T. G. Daniels, X. Wang, A. Paul, J. Lin, B. M. Spiegelman, S. C. Stevenson, and S. M. Rangwala Muscle-specific expression of PPAR{gamma} coactivator-1{alpha} improves exercise performance and increases peak oxygen uptake J Appl Physiol, May 1, 2008; 104(5): 1304 - 1312. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Pilegaard and E. A. Richter PGC-1{alpha}: important for exercise performance? J Appl Physiol, May 1, 2008; 104(5): 1264 - 1265. [Full Text] [PDF] |
||||
![]() |
Z He, Y Hu, L Feng, Y Li, G Liu, Y Xi, L Wen, and A Lucia NRF-1 genotypes and endurance exercise capacity in young Chinese men Br. J. Sports Med., May 1, 2008; 42(5): 361 - 366. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C. Scarpulla Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function Physiol Rev, April 1, 2008; 88(2): 611 - 638. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Arany, B. K. Wagner, Y. Ma, J. Chinsomboon, D. Laznik, and B. M. Spiegelman Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1{alpha} and oxidative phosphorylation PNAS, March 25, 2008; 105(12): 4721 - 4726. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. T. Morris, M. J. Laye, S. J. Lees, R. S. Rector, J. P. Thyfault, and F. W. Booth Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat J Appl Physiol, March 1, 2008; 104(3): 708 - 715. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. De Filippis, G. Alvarez, R. Berria, K. Cusi, S. Everman, C. Meyer, and L. J. Mandarino Insulin-resistant muscle is exercise resistant: evidence for reduced response of nuclear-encoded mitochondrial genes to exercise Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E607 - E614. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-a Kim, Y. Wei, and J. R. Sowers Role of Mitochondrial Dysfunction in Insulin Resistance Circ. Res., February 29, 2008; 102(4): 401 - 414. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. R. Short, N. Moller, M. L. Bigelow, J. Coenen-Schimke, and K. S. Nair Enhancement of Muscle Mitochondrial Function by Growth Hormone J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 597 - 604. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. M. Thomson, S. T. Herway, N. Fillmore, H. Kim, J. D. Brown, J. R. Barrow, and W. W. Winder AMP-activated protein kinase phosphorylates transcription factors of the CREB family J Appl Physiol, February 1, 2008; 104(2): 429 - 438. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. J. Green, T. A. Duhamel, G. P. Holloway, J. W. Moule, D. W. Ranney, A. R. Tupling, and J. Ouyang Rapid upregulation of GLUT-4 and MCT-4 expression during 16 h of heavy intermittent cycle exercise Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R594 - R600. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Leick, J. F. P. Wojtaszewski, S. T. Johansen, K. Kiilerich, G. Comes, Y. Hellsten, J. Hidalgo, and H. Pilegaard PGC-1{alpha} is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E463 - E474. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. R. Wende, P. J. Schaeffer, G. J. Parker, C. Zechner, D.-H. Han, M. M. Chen, C. R. Hancock, J. J. Lehman, J. M. Huss, D. A. McClain, et al. A Role for the Transcriptional Coactivator PGC-1{alpha} in Muscle Refueling J. Biol. Chem., December 14, 2007; 282(50): 36642 - 36651. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Walter and F. Seebacher Molecular mechanisms underlying the development of endothermy in birds (Gallus gallus): a new role of PGC-1{alpha}? Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2007; 293(6): R2315 - R2322. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. H. Mortensen, P. Plomgaard, C. P. Fischer, A. K. Hansen, H. Pilegaard, and B. K. Pedersen PGC-1beta is downregulated by training in human skeletal muscle: no effect of training twice every second day vs. once daily on expression of the PGC-1 family J Appl Physiol, November 1, 2007; 103(5): 1536 - 1542. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Canto, S. Pich, J. C. Paz, R. Sanches, V. Martinez, M. Orpinell, M. Palacin, A. Zorzano, and A. Guma Neuregulins Increase Mitochondrial Oxidative Capacity and Insulin Sensitivity in Skeletal Muscle Cells Diabetes, September 1, 2007; 56(9): 2185 - 2193. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. J. Adhihetty, T. Taivassalo, R. G. Haller, D. R. Walkinshaw, and D. A. Hood The effect of training on the expression of mitochondrial biogenesis- and apoptosis-related proteins in skeletal muscle of patients with mtDNA defects Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E672 - E680. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Schiaffino, M. Sandri, and M. Murgia Activity-Dependent Signaling Pathways Controlling Muscle Diversity and Plasticity Physiology, August 1, 2007; 22(4): 269 - 278. [Abstract] [Full Text] [PDF] |
||||
![]() |
T.-Y. Lee, K.-L. Tsai, W.-S. Lee, and C. Hsu The molecular events occur during MK-801-induced cytochrome oxidase subunit II down-regulation in GT1-7 cells J. Mol. Endocrinol., July 1, 2007; 39(1): 53 - 66. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Miura, K. Kawanaka, Y. Kai, M. Tamura, M. Goto, T. Shiuchi, Y. Minokoshi, and O. Ezaki An Increase in Murine Skeletal Muscle Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha} (PGC-1{alpha}) mRNA in Response to Exercise Is Mediated by {beta}-Adrenergic Receptor Activation Endocrinology, July 1, 2007; 148(7): 3441 - 3448. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. C. Smith, K. L. Mullen, K. A. Junkin, J. Nickerson, A. Chabowski, A. Bonen, and D. J. Dyck Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E172 - E181. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. C. Wright, P. C. Geiger, D.-H. Han, T. E. Jones, and J. O. Holloszy Calcium Induces Increases in Peroxisome Proliferator-activated Receptor {gamma} Coactivator-1{alpha} and Mitochondrial Biogenesis by a Pathway Leading to p38 Mitogen-activated Protein Kinase Activation J. Biol. Chem., June 29, 2007; 282(26): 18793 - 18799. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Garcia-Roves, J. M. Huss, D.-H. Han, C. R. Hancock, E. Iglesias-Gutierrez, M. Chen, and J. O. Holloszy Raising plasma fatty acid concentration induces increased biogenesis of mitochondria in skeletal muscle PNAS, June 19, 2007; 104(25): 10709 - 10713. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. N. Finck and D. P. Kelly Peroxisome Proliferator-Activated Receptor {gamma} Coactivator-1 (PGC-1) Regulatory Cascade in Cardiac Physiology and Disease Circulation, May 15, 2007; 115(19): 2540 - 2548. [Full Text] [PDF] |
||||
![]() |
D. C. Wright, D.-H. Han, P. M. Garcia-Roves, P. C. Geiger, T. E. Jones, and J. O. Holloszy Exercise-induced Mitochondrial Biogenesis Begins before the Increase in Muscle PGC-1{alpha} Expression J. Biol. Chem., January 5, 2007; 282(1): 194 - 199. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. D. Wadley and G. K. McConell Effect of nitric oxide synthase inhibition on mitochondrial biogenesis in rat skeletal muscle J Appl Physiol, January 1, 2007; 102(1): 314 - 320. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Sacheck, J.-P. K. Hyatt, A. Raffaello, R. T. Jagoe, R. R. Roy, V. R. Edgerton, S. H. Lecker, and A. L. Goldberg Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases FASEB J, January 1, 2007; 21(1): 140 - 155. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Devin and M. Rigoulet Mechanisms of mitochondrial response to variations in energy demand in eukaryotic cells Am J Physiol Cell Physiol, January 1, 2007; 292(1): C52 - C58. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Handschin and B. M. Spiegelman Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1 Coactivators, Energy Homeostasis, and Metabolism Endocr. Rev., December 1, 2006; 27(7): 728 - 735. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Liang and W. F. Ward PGC-1{alpha}: a key regulator of energy metabolism Advan Physiol Educ, December 1, 2006; 30(4): 145 - 151. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Sandri, J. Lin, C. Handschin, W. Yang, Z. P. Arany, S. H. Lecker, A. L. Goldberg, and B. M. Spiegelman PGC-1{alpha} protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription PNAS, October 31, 2006; 103(44): 16260 - 16265. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Nichol, M. Christian, J. H. Steel, R. White, and M. G. Parker RIP140 Expression Is Stimulated by Estrogen-related Receptor {alpha} during Adipogenesis J. Biol. Chem., October 27, 2006; 281(43): 32140 - 32147. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. H. Mortensen, L. Frandsen, P. Schjerling, E. Nishimura, and N. Grunnet PGC-1{alpha} and PGC-1beta have both similar and distinct effects on myofiber switching toward an oxidative phenotype Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E807 - E816. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Wu, X. Huang, Y. Feng, C. Handschin, Y. Feng, P. S. Gullicksen, O. Bare, M. Labow, B. Spiegelman, and S. C. Stevenson Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1{alpha} transcription and mitochondrial biogenesis in muscle cells PNAS, September 26, 2006; 103(39): 14379 - 14384. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Baker, A. C. Betik, D. J. Krause, and R. T. Hepple No decline in skeletal muscle oxidative capacity with aging in long-term calorically restricted rats: effects are independent of mitochondrial DNA integrity. J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2006; 61(7): 675 - 684. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Reznick and G. I. Shulman The role of AMP-activated protein kinase in mitochondrial biogenesis J. Physiol., July 1, 2006; 574(1): 33 - 39. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Arany, M. Novikov, S. Chin, Y. Ma, A. Rosenzweig, and B. M. Spiegelman Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-{gamma} coactivator 1{alpha} PNAS, June 27, 2006; 103(26): 10086 - 10091. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Hood, I. Irrcher, V. Ljubicic, and A.-M. Joseph Coordination of metabolic plasticity in skeletal muscle J. Exp. Biol., June 15, 2006; 209(12): 2265 - 2275. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M. Garcia-Roves, J. Huss, and J. O. Holloszy Role of calcineurin in exercise-induced mitochondrial biogenesis Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1172 - E1179. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. G. Coffey, A. Shield, B. J. Canny, K. A. Carey, D. Cameron-Smith, and J. A. Hawley Interaction of contractile activity and training history on mRNA abundance in skeletal muscle from trained athletes Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E849 - E855. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Terada, S. Wicke, J. O. Holloszy, and D.-H. Han PPAR{delta} activator GW-501516 has no acute effect on glucose transport in skeletal muscle Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E607 - E611. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. R. Benton, X.-X. Han, M. Febbraio, T. E. Graham, and A. Bonen Inverse relationship between PGC-1{alpha} protein expression and triacylglycerol accumulation in rodent skeletal muscle J Appl Physiol, February 1, 2006; 100(2): 377 - 383. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. R. Wende, J. M. Huss, P. J. Schaeffer, V. Giguere, and D. P. Kelly PGC-1{alpha} Coactivates PDK4 Gene Expression via the Orphan Nuclear Receptor ERR{alpha}: a Mechanism for Transcriptional Control of Muscle Glucose Metabolism Mol. Cell. Biol., December 15, 2005; 25(24): 10684 - 10694. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Choi, X. Liu, P. Li, T. Akimoto, S. Y. Lee, M. Zhang, and Z. Yan Transcriptional profiling in mouse skeletal muscle following a single bout of voluntary running: evidence of increased cell proliferation J Appl Physiol, December 1, 2005; 99(6): 2406 - 2415. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. B. Taylor, J. D. Lamb, R. W. Hurst, D. G. Chesser, W. J. Ellingson, L. J. Greenwood, B. B. Porter, S. T. Herway, and W. W. Winder Endurance training increases skeletal muscle LKB1 and PGC-1{alpha} protein abundance: effects of time and intensity Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E960 - E968. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. J. Cluberton, S. L. McGee, R. M. Murphy, and M. Hargreaves Effect of carbohydrate ingestion on exercise-induced alterations in metabolic gene expression J Appl Physiol, October 1, 2005; 99(4): 1359 - 1363. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Ojaimi, W. Li, S. Kinugawa, H. Post, A. Csiszar, P. Pacher, G. Kaley, and T. H. Hintze Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: heart failure and the fetal phenotype Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1399 - H1407. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. R. Koves, P. Li, J. An, T. Akimoto, D. Slentz, O. Ilkayeva, G. L. Dohm, Z. Yan, C. B. Newgard, and D. M. Muoio Peroxisome Proliferator-activated Receptor-{gamma} Co-activator 1{alpha}-mediated Metabolic Remodeling of Skeletal Myocytes Mimics Exercise Training and Reverses Lipid-induced Mitochondrial Inefficiency J. Biol. Chem., September 30, 2005; 280(39): 33588 - 33598. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Cartoni, B. Leger, M. B. Hock, M. Praz, A. Crettenand, S. Pich, J.-L. Ziltener, F. Luthi, O. Deriaz, A. Zorzano, et al. Mitofusins 1/2 and ERR{alpha} expression are increased in human skeletal muscle after physical exercise J. Physiol., August 15, 2005; 567(1): 349 - 358. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Lucia, F. Gomez-Gallego, I. Barroso, M. Rabadan, F. Bandres, A. F. San Juan, J. L. Chicharro, U. Ekelund, S. Brage, C. P. Earnest, et al. PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men J Appl Physiol, July 1, 2005; 99(1): 344 - 348. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Akimoto, S. C. Pohnert, P. Li, M. Zhang, C. Gumbs, P. B. Rosenberg, R. S. Williams, and Z. Yan Exercise Stimulates Pgc-1{alpha} Transcription in Skeletal Muscle through Activation of the p38 MAPK Pathway J. Biol. Chem., May 20, 2005; 280(20): 19587 - 19593. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. E. Padfield, L. G. Astrakas, Q. Zhang, S. Gopalan, G. Dai, M. N. Mindrinos, R. G. Tompkins, L. G. Rahme, and A. A. Tzika Burn injury causes mitochondrial dysfunction in skeletal muscle PNAS, April 12, 2005; 102(15): 5368 - 5373. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M. Garcia-Roves, T. E. Jones, K. Otani, D.-H. Han, and J. O. Holloszy Calcineurin Does Not Mediate Exercise-Induced Increase in Muscle GLUT4 Diabetes, March 1, 2005; 54(3): 624 - 628. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Garnier, D. Fortin, J. Zoll, B. N'Guessan, B. Mettauer, E. Lampert, V. Veksler, and R. Ventura-Clapier Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle FASEB J, January 1, 2005; 19(1): 43 - 52. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Akimoto, T. J. Ribar, R. S. Williams, and Z. Yan Skeletal muscle adaptation in response to voluntary running in Ca2+/calmodulin-dependent protein kinase IV-deficient mice Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1311 - C1319. [Abstract] [Full Text] [PDF] |
||||
![]() |
|