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Prediction of Muscle Energy States at Low Metabolic Rates Requires Feedback Control of Mitochondrial Respiratory Chain Activity by Inorganic Phosphate

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Listed:
  • Joep P J Schmitz
  • Jeroen A L Jeneson
  • Joep W M van Oorschot
  • Jeanine J Prompers
  • Klaas Nicolay
  • Peter A J Hilbers
  • Natal A W van Riel

Abstract

The regulation of the 100-fold dynamic range of mitochondrial ATP synthesis flux in skeletal muscle was investigated. Hypotheses of key control mechanisms were included in a biophysical model of oxidative phosphorylation and tested against metabolite dynamics recorded by 31P nuclear magnetic resonance spectroscopy (31P MRS). Simulations of the initial model featuring only ADP and Pi feedback control of flux failed in reproducing the experimentally sampled relation between myoplasmic free energy of ATP hydrolysis (ΔGp = ΔGpo′+RT ln ([ADP][Pi]/[ATP]) and the rate of mitochondrial ATP synthesis at low fluxes (

Suggested Citation

  • Joep P J Schmitz & Jeroen A L Jeneson & Joep W M van Oorschot & Jeanine J Prompers & Klaas Nicolay & Peter A J Hilbers & Natal A W van Riel, 2012. "Prediction of Muscle Energy States at Low Metabolic Rates Requires Feedback Control of Mitochondrial Respiratory Chain Activity by Inorganic Phosphate," PLOS ONE, Public Library of Science, vol. 7(3), pages 1-14, March.
    • Handle: RePEc:plo:pone00:0034118
    DOI: 10.1371/journal.pone.0034118
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    1. Hiroaki Kitano, 2002. "Computational systems biology," Nature, Nature, vol. 420(6912), pages 206-210, November.
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