Control and Regulation of Integrated Mitochondrial Function in Metabolic and Transport Networks

International Journal of Molecular Sciences

Sonia Cortassa¹  Brian O’Rourke¹  Raimond L. Winslow² 

[1] Johns Hopkins University, School of Medicine, Division of Cardiology 720 Rutland Ave, 1059 Ross Bldg, Baltimore, MD 21205, USA; E-Mails:;Institute for Computational Medicine, 3400 N. Charles St. CSEB 315, Baltimore, MD 21218, USA; E-Mail:

关键词: Mitochondrial computational model;    mitochondrial energetics;    excitation-contraction coupling;    calcium dynamics;    metabolic control analysis;    distributed control;    control by diffuse loops;   

DOI  :  10.3390/ijms10041500

来源: mdpi

【 摘 要 】

The pattern of flux and concentration control coefficients in an integrated mitochondrial energetics model is examined by applying a generalized matrix method of control analysis to calculate control coefficients, as well as response coefficients The computational model of Cortassa et al. encompasses oxidative phosphorylation, the TCA cycle, and Ca²⁺ dynamics. Control of ATP synthesis, TCA cycle, and ANT fluxes were found to be distributed among various mitochondrial processes. Control is shared by processes associated with ATP/ADP production and transport, as well as by Ca²⁺ dynamics. The calculation also analyzed the control of the concentrations of key regulatory ions and metabolites (Ca²⁺, NADH, ADP). The approach we have used demonstrates how properties of integrated systems may be understood through applications of computational modeling and control analysis.

【 授权许可】

CC BY   
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.