a biophysical model of the mitochondrial respiratory system and oxidative phosphorylation的生物物理模型线粒体呼吸系统和氧化磷酸化.pdf

A Biophysical Model of the Mitochondrial Respiratory System and Oxidative Phosphorylation Daniel A. Beard Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America A computational model for the mitochondrial respiratory chain that appropriately balances mass, charge, and free energy transduction is introduced and analyzed based on a previously published set of data measured on isolated cardiac mitochondria. The basic components included in the model are the reactions at complexes I, III, and IV of the electron transport system, ATP synthesis at F1F0 ATPase, substrate transporters including adenine nucleotide translocase and the phosphate–hydrogen co-transporter, and cation fluxes across the inner membrane including fluxes through the Kþ/Hþ antiporter and passive Hþ and Kþ permeation. Estimation of 16 adjustable parameter values is based on fitting model simulations to nine independent data curves. The identified model is further validated by comparison to additional datasets measured from mitochondria isolated from rat heart and liver and observed at low oxygen concentration. To obtain reasonable fits to the available data, it is necessary to incorporate inorganic-phosphate- dependent activation of the dehydrogenase activity and the electron transport system. Specifically, it is shown that a model incorporating phosphate-dependent activation of complex III is able to reasonably reproduce the observed data. The resulting validated and verified model provides a foundation for building larger and more complex systems models and investigating complex physiological and pathophysiological interactions in cardiac energetics. Citation: Beard DA (2005) A biophysical model of the mitochondrial respiratory system and oxidative phosphorylation. PLoS Comput Biol