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Control and Regulation of Integrated Mitochondrial Function in Metabolic and Transport Networks
Johns Hopkins University, School of Medicine, Division of Cardiology 720 Rutland Ave, 1059 Ross Bldg, Baltimore, MD 21205, USA
Institute for Computational Medicine, 3400 N. Charles St. CSEB 315, Baltimore, MD 21218, USA
* Author to whom correspondence should be addressed.
Received: 21 February 2009; in revised form: 26 March 2009 / Accepted: 30 March 2009 / Published: 1 April 2009
Abstract: 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.
Keywords: Mitochondrial computational model; mitochondrial energetics; excitation-contraction coupling; calcium dynamics; metabolic control analysis; distributed control; control by diffuse loops.
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Cortassa, S.; O’Rourke, B.; Winslow, R.L.; Aon, M.A. Control and Regulation of Integrated Mitochondrial Function in Metabolic and Transport Networks. Int. J. Mol. Sci. 2009, 10, 1500-1513.
Cortassa S, O’Rourke B, Winslow RL, Aon MA. Control and Regulation of Integrated Mitochondrial Function in Metabolic and Transport Networks. International Journal of Molecular Sciences. 2009; 10(4):1500-1513.
Cortassa, Sonia; O’Rourke, Brian; Winslow, Raimond L.; Aon, Miguel A. 2009. "Control and Regulation of Integrated Mitochondrial Function in Metabolic and Transport Networks." Int. J. Mol. Sci. 10, no. 4: 1500-1513.