Comprehensive mathematical model of oxidative phosphorylation valid for physiological and pathological conditions

FEBS J. 2017 Sep;284(17):2802-2828. doi: 10.1111/febs.14151. Epub 2017 Jul 25.


We developed a mathematical model of oxidative phosphorylation (OXPHOS) that allows for a precise description of mitochondrial function with respect to the respiratory flux and the ATP production. The model reproduced flux-force relationships under various experimental conditions (state 3 and 4, uncoupling, and shortage of respiratory substrate) as well as time courses, exhibiting correct P/O ratios. The model was able to reproduce experimental threshold curves for perturbations of the respiratory chain complexes, the F1 F0 -ATP synthase, the ADP/ATP carrier, the phosphate/OH carrier, and the proton leak. Thus, the model is well suited to study complex interactions within the OXPHOS system, especially with respect to physiological adaptations or pathological modifications, influencing substrate and product affinities or maximal catalytic rates. Moreover, it could be a useful tool to study the role of OXPHOS and its capacity to compensate or enhance physiopathologies of the mitochondrial and cellular energy metabolism.

Keywords: enzyme kinetics; mathematical modeling; oxidative phosphorylation; proton motive force; threshold curves.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Algorithms
  • Animals
  • Biocatalysis
  • Cattle
  • Kinetics
  • Metabolic Flux Analysis
  • Mitochondria, Heart / metabolism
  • Models, Biological*
  • Oxidative Phosphorylation*


  • Adenosine Triphosphate