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Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle

Published online by Cambridge University Press:  05 March 2007

Edward O. Ojuka
Edward O. Ojuka*
Affiliation:
Department of Human Biology, University of Cape Town, Cape Town, 7700, South Africa
*
Corresponding author: Dr Edward O. Ojuka Fax: +27 21 6867530, Email: [email protected]
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Abstract

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Contractile activity induces mitochondrial biogenesis and increases glucose transport capacity in muscle. There has been much research on the mechanisms responsible for these adaptations. The present paper reviews the evidence, which indicates that the decrease in the levels of high-energy phosphates, leading to activation of AMP kinase (AMPK), and the increase in cytosolic Ca2+, which activates Ca2+/calmodulin-dependent protein kinase (CAMK), are signals that initiate these adaptative responses. Although the events downstream of AMPK and CAMK have not been well characterized, these events lead to activation of various transcription factors, including: nuclear respiratory factors (NRF) 1 and 2, which cause increased expression of proteins of the respiratory chain; PPAR-α, which up regulates the levels of enzymes of β oxidation; mitochondrial transcription factor A, which activates expression of the mitochondrial genome; myocyte-enhancing factor 2A, the transcription factor that regulates GLUT4 expression. The well-orchestrated expression of the multitude of proteins involved in these adaptations is mediated by the rapid activation of PPARγ co-activator (PGC) 1, a protein that binds to various transcription factors to maximize transcriptional activity. Activating AMPK using 5-aminoimidizole-4-carboxamide-1-β-D-riboside (AICAR) and increasing cytoplasmic Ca2+using caffeine, W7 or ionomycin in L6 myotubes increases the concentration of mitochondrial enzymes and GLUT4 and enhances the binding of NRF-1 and NRF-2 to DNA. AICAR and Ca-releasing agents also increase the levels of PGC-1, mitochondrial transcription factor A and myocyte-enhancing factors 2A and 2D. These results are similar to the responses seen in muscle during the adaptation to endurance exercise and show that L6 myotubes are a suitable model for studying the mechanisms by which exercise causes the adaptive responses in muscle mitochondria and glucose transport.

Keywords

Mitochondrial biogenesisGLUT4Ca2+/calmodulin-dependent protein kinaseAMP kinaseTranscription factors
Type
Symposium 3: Mechanisms involved in exercise-induced mitochondrila biogenesis in skeletal muscle
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 2 , May 2004 , pp. 275 - 278
Copyright
Copyright © The Nutrition Society 2004

References

Baar, K, Wende, AR, Jones, TE, Marison, M, Nolte, LA, Chen, M, Kelly, DP & Holloszy, JO (2002) Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB Journal 16, 1879–1886.CrossRefGoogle ScholarPubMed
Bergeron, R, Ren, JM, Cadman, KS, Moore, IK, Perret, P, Pypaert, M, Young, LH, Semenkovich, CF & Shulman, GI (2001) Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. American Journal of Physiology 281, E1340–E1346.Google ScholarPubMed
Briadotti, G, Borthwick, IA & May, BK (1993) Identification of regulatory sequences in the gene for 5-aminolevulinate synthase from rat. Journal of Biological Chemistry 268, 1109–1117.CrossRefGoogle Scholar
Corcoran, EE & Mean, AR (2001) Defining Ca 2+ /calmodulin-dependent protein kinase cascade in transcriptional regulation. Journal of Biological Chemistry 276, 2975–2978.Google Scholar
Freyssenet, D Di Carlo, M & Hood, DA (1999) Calcium-dependent regulation of cytochrome c gene expression in skeletal muscle cells. Journal of Biological Chemistry 274, 9305–9311.Google Scholar
Fryer, LG, Foufella, F, Barnes, K, Baldwin, SA, Woods, A & Carling, D (2002) Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells. Biochemical Journal 363, 167–174.CrossRefGoogle ScholarPubMed
Hawley, SA, Selbert, MA, Goldstein, EG, Edelman, AM, Carling, D & Hardie, DG (1995) 5‘-AMP activated protein kinase cascade, and Ca 2+ /calmodulin activates the calmodulin-dependent protein kinase I kinase, via three independent mechanisms. Journal of Biological Chemistry 270, 27186–27191.Google Scholar
Hayashi, T, Hirshman, MF, Kurth, EJ, Winder, WW & Goodyear, LJ (1998) Evidence for 5‘ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 49, 1369–1373.Google Scholar
Holloszy, JO & Booth, FW (1976) Biochemical adaptations to endurance exercise in muscle. Annual Review of Physiology 38, 273–291.Google Scholar
Holmes, BF, Kurth-Kraczek, EJ & Winder, WW (1999) Chronic activation of 5‘-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle. Journal of Applied Physiology 87, 1990–1995.Google Scholar
Hood, DA (2001) Plasticity in skeletal, cardiac, and smooth muscle. Contractile activity-induced mitochondrial biogenesis in skeletal muscle. Journal of Applied Physiology 90, 1137–1157.Google Scholar
Lawrence, JC Jr & Salsgiver, WJ (1983) Levels of enzymes of energy metabolism are controlled by activity of cultured rat myotubes. American Journal of Physiology 244, C348–C355.CrossRefGoogle ScholarPubMed
Neufer, PD & Dohm, GL (1993) Exercise induces a transient increase in transcription of the GLUT-4 gene in skeletal muscle. American Journal of Physiology 265, C1597–C1603.Google Scholar
Ojuka, EO, Jones, TE, Han, DH, Chen, M & Holloszy, JO (2003) Raising Ca 2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle. FASEB Journal 17, 675–681.CrossRefGoogle Scholar
Ojuka, EO, Jones, TE, Han, DH, Chen, M, Wanhoff, BR, Sturek, M & Holloszy, JO (2002 a) Intermittent increases in cytosolic Ca 2+ stimulate mitochondrial biogenesis in muscle cells. American Journal of Physiology 283, E1040–E1045.Google Scholar
Ojuka, EO, Jones, TE, Nolte, LA, Chen, M, Wonhoff, BR, Sturek, M & Holloszy, JO (2002 b) Regulation of GLUT-4 biogenesis: evidence for involvement of AMPK and Ca 2+. American Journal of Physiology 282, E1008–E1013.Google Scholar
Ojuka, EO, Nolte, LA & Holloszy, JO (2000) Increased expression of GLUT-4 and hexokinase in rat epitroclearis muscle exposed to AICAR in vitro. Journal of Applied Physiology 88, 1072–1075.CrossRefGoogle Scholar
Oshel, KM, Knight, JB, Cao, KT, Thai, MV & Olson, AL (2000) Identification of a 30 base pair regulatory element and a novel DNA binding protein that regulates the human GLUT-4 promoter in transgenic mice. Journal of Biological Chemistry 275, 23666–23673.Google Scholar
Puigserver, P, Wu, Z, Park, CW, Graves, R, Wright, M & Spiegelman, BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92, 829–839.Google Scholar
Ren, JM, Semenkovich, CF, Gulve, EA, Gao, EA & Holloszy, JO (1994) Exercise induces rapid increases in GLUT-4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscle. Journal of Biological Chemistry 269, 14396–14401.Google Scholar
Salt, I, Celler, JW, Hawley, SA, Prescott, A & Woods, A (1998) AMP-activated protein kinase: greater AMP dependence, and preferential nuclear localization, of complexes containing alpha2 isoform. Biochemical Journal 334, 177–187.Google Scholar
Scarpulla, RC (2002) Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochimica et Biophysica Acta 1576, 1–14.CrossRefGoogle ScholarPubMed
Terada, S, Yokozeki, T, Kawanaka, K, Ogawa, K, Higuchi, M, Ezaki, O & Tabata, I (2001) Effects of high-intensity swimming training on GLUT-4 and glucose transport activity in rat skeletal muscle. Journal of Applied Physiology 90, 2019–2024.Google Scholar
Vega, R, Huss, JM & Kelly, DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor α in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Molecular and Cellular Biology 20, 1868–1876.CrossRefGoogle ScholarPubMed
Virbasius, JV & Scarpulla, RC (1994) Activation of the human transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Proceedings of the National Academy of Sciences USA 91, 1309–1313.Google Scholar
Winder, WW & Hardie, DG (1999) AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. American Journal of Physiology 277, E1–E10.Google Scholar
Winder, WW, Holmes, BF, Rubink, DS, Jensen, EB, Chen, M & Holloszy, JO (2000) Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscles. Journal of Applied Physiology 88, 2219–2226.CrossRefGoogle Scholar
Wu, H, Kanatous, SB, Thumond, FA, Gallardo, T, Isotani, E, Bassel-Durby, R & Williams, RS (2002) Regulation of mitochondrial biogenesis in skeletal muscle in CAMK. Science 296, 349–352.Google Scholar
Wu, Z, Puisgsever, P, Anderson, U, Zhang, C, Adelmant, G, Moother, V, Troy, A, Cinti, S, Lowell, B, Scarpulla, RC & Speigelman, BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115–124.CrossRefGoogle ScholarPubMed
Yaspelkis, BB, Castle, AL, Farrar, RP & Ivy, JL (1997) Contraction-induced intercellular signals and their relationship to muscle GLUT-4 concentration. American Journal of Physiology 272, E118–E125.Google Scholar
Zheng, D, MacLean, PS, Pohnert, SC, Knight, JB, Olson, AL, Winder, WW & Dhom, GL (2001) Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase. Journal of Applied Physiology 91, 1073–1083.CrossRefGoogle ScholarPubMed