Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement

Edwin Janssen, Petras P. Dzeja, Frank Oerlemans, Arjan W. Simonetti, Arend Heerschap, Arnold De Haan, Paula S. Rush, Ronald R. Terjung, Bé Wieringa, Andre Terzic

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

Efficient cellular energy homeostasis is a critical determinant of muscle performance, providing evolutionary advantages responsible for species survival. Phosphotransfer reactions, which couple ATP production and utilization, are thought to play a central role in this process. Here, we provide evidence that genetic disruption of AK1-catalyzed β-phosphoryl transfer in mice decreases the potential of myofibers to sustain nucleotide ratios despite up-regulation of high-energy phosphoryl flux through glycolytic, guanylate and creatine kinase phosphotransfer pathways. A maintained contractile performance of AK1-deficient muscles was associated with higher ATP turnover rate and larger amounts of ATP consumed per contraction. Metabolic stress further aggravated the energetic cost in AK1(-/-) muscles. Thus, AK1-catalyzed phosphotransfer is essential in the maintenance of cellular energetic economy, enabling skeletal muscle to perform at the lowest metabolic cost.

Original languageEnglish (US)
Pages (from-to)6371-6381
Number of pages11
JournalEMBO Journal
Volume19
Issue number23
DOIs
StatePublished - Dec 1 2000

Keywords

  • Adenylate kinase
  • Creatine kinase
  • Energy homeostasis
  • Knockout mice
  • Phosphoryl transfer

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Janssen, E., Dzeja, P. P., Oerlemans, F., Simonetti, A. W., Heerschap, A., De Haan, A., Rush, P. S., Terjung, R. R., Wieringa, B., & Terzic, A. (2000). Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement. EMBO Journal, 19(23), 6371-6381. https://doi.org/10.1093/emboj/19.23.6371