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

108 Citations (Scopus)

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
StatePublished - Dec 1 2000

Fingerprint

Gene Deletion
Muscle
Genes
Adenosine Triphosphate
Muscles
Guanylate Kinases
Costs and Cost Analysis
Physiological Stress
Creatine Kinase
Skeletal Muscle
Homeostasis
Up-Regulation
Nucleotides
Maintenance
Costs
Fluxes
adenylate kinase 1

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Janssen, E., Dzeja, P. P., Oerlemans, F., Simonetti, A. W., Heerschap, A., De Haan, A., ... Terzic, A. (2000). Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement. EMBO Journal, 19(23), 6371-6381.

Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement. / Janssen, Edwin; Dzeja, Petras P; Oerlemans, Frank; Simonetti, Arjan W.; Heerschap, Arend; De Haan, Arnold; Rush, Paula S.; Terjung, Ronald R.; Wieringa, Bé; Terzic, Andre.

In: EMBO Journal, Vol. 19, No. 23, 01.12.2000, p. 6371-6381.

Research output: Contribution to journalArticle

Janssen, E, Dzeja, PP, Oerlemans, F, Simonetti, AW, Heerschap, A, De Haan, A, Rush, PS, Terjung, RR, Wieringa, B & Terzic, A 2000, 'Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement', EMBO Journal, vol. 19, no. 23, pp. 6371-6381.
Janssen E, Dzeja PP, Oerlemans F, Simonetti AW, Heerschap A, De Haan A et al. Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement. EMBO Journal. 2000 Dec 1;19(23):6371-6381.
Janssen, Edwin ; Dzeja, Petras P ; Oerlemans, Frank ; Simonetti, Arjan W. ; Heerschap, Arend ; De Haan, Arnold ; Rush, Paula S. ; Terjung, Ronald R. ; Wieringa, Bé ; Terzic, Andre. / Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement. In: EMBO Journal. 2000 ; Vol. 19, No. 23. pp. 6371-6381.
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