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Mitochondrial biogenesis in fast skeletal muscle of CK deficient mice: Mitochondrial biogenesis in CK deficient mice

Abstract : Creatine kinase (CK) is a phosphotransfer kinase that catalyzes the reversible transfer of a phosphate moiety between ADP and creatine and that is highly expressed in skeletal muscle. In fast glycolytic skeletal muscle, deletion of the cytosolic M isoform of CK in mice (M-CK-/-) leads to a massive increase in the oxidative capacity and of mitochondrial volume. This study was aimed at investigating the transcriptional pathways leading to mitochondrial biogenesis in response to CK deficiency. Wild type and M-CK-/- mice of eleven months of age were used for this study. Gastrocnemius muscles of M-CK-/- mice exhibited a dramatic increase in citrate synthase (+120%) and cytochrome oxidase (COX, +250%) activity, and in mitochondrial DNA (+60%), showing a clear activation of mitochondrial biogenesis. Similarly, mRNA expression of the COXI (mitochondria-encoded) and COXIV (nuclear-encoded) subunits were increased by +103 and +94 % respectively. This was accompanied by an increase in the expression of the nuclear respiratory factor (NRF2Α and the mitochondrial transcription factor (mtTFA). Expression of the co-activator PGC-1Α, a master gene in mitochondrial biogenesis was not significantly increased while that of PGC-1Β and PRC, two members of the same family, was moderately increased (+45% and +55% respectively). While the expression of the modulatory calcineurin-interacting protein 1 (MCIP1) was dramatically decreased (minus 68%) suggesting inactivation of the calcineurin pathway, the metabolic sensor AMPK was activated (+86%) in M-CK-/- mice. These results evidence that mitochondrial biogenesis in response to a metabolic challenge exhibits a unique pattern of regulation, involving activation of the AMPK pathway.
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Contributor : Renée Ventura-Clapier <>
Submitted on : Tuesday, June 24, 2008 - 5:10:11 PM
Last modification on : Wednesday, September 16, 2020 - 4:54:17 PM
Long-term archiving on: : Friday, May 28, 2010 - 10:48:54 PM


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  • HAL Id : inserm-00290139, version 1
  • PUBMED : 18054321



Anika Vaarmann, Dominique Fortin, Vladimir Veksler, Iman Momken, Renée Ventura-Clapier, et al.. Mitochondrial biogenesis in fast skeletal muscle of CK deficient mice: Mitochondrial biogenesis in CK deficient mice. Biochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics, Elsevier, 2008, 777 ((1)), pp.39-47. ⟨inserm-00290139⟩



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