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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: eojuka@sports.uct.ac.za
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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

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