NDLI: Dynamic Simulation of Mitochondrial Respiration and Oxidative Phosphorylation: Comparison with Experimental Results

Content Provider	Springer Nature Link
Author	Guillaud, François Hannaert, Patrick
Copyright Year	2008
Abstract	Hypoxia hampers ATP production and threatens cell survival. Since cellular energetics tightly controls cell responses and fate, ATP levels and dynamics are of utmost importance. An integrated mathematical model of ATP synthesis by the mitochondrial oxidative phosphorylation/electron transfer chain system has been recently published (Beard, PLoS Comput Biol 1(4):e36, 2005). This model was validated under static conditions. To evaluate its performance under dynamical situations, we implemented and simulated it (Simulink®, The Mathworks). Inner membrane potential (ΔΨ) and [NADH] (feeding the electron transfer chain) were used as indicators of mitochondrial function. Root mean squared error (rmse) was used to compare simulations and experiments (isolated cardiac mitochondria, Bose et al. J Biol Chem 278(40):39155–39165, 2003). Steady-state experimental data were reproduced within 2–6%. Model dynamics were evaluated under: (i) baseline, (ii) activation of NADH production, (iii) addition of ADP, (iv) addition of inorganic phosphate, (v) oxygen exhaustion. In all phases, except the last one, ΔΨ and [NADH] as well as oxygen consumption, were reproduced (within 10, 7 and 12%, respectively). Under anoxia, simulated ΔΨ markedly depolarized (no change in experiments). In conclusion, the model reproduces dynamic data as long as oxygen is present. Anticipated improvement by the inclusion of ATP consumption and explicit Krebs cycle are under evaluation.
Starting Page	157
Ending Page	172
Page Count	16
File Format	PDF
ISSN	00015342
Journal	Acta Biotheoretica
Volume Number	56
Issue Number	1-2
e-ISSN	15728358
Language	English
Publisher	Springer Netherlands
Publisher Date	2008-01-30
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Evolutionary Biology Philosophy of Biology
Content Type	Text
Resource Type	Article
Subject	Philosophy Applied Mathematics Medicine Biochemistry, Genetics and Molecular Biology Environmental Science Agricultural and Biological Sciences

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