Int. J. Mol. Sci. 2009, 10(4), 1500-1513; doi:10.3390/ijms10041500
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Control and Regulation of Integrated Mitochondrial Function in Metabolic and Transport Networks

1 Johns Hopkins University, School of Medicine, Division of Cardiology 720 Rutland Ave, 1059 Ross Bldg, Baltimore, MD 21205, USA 2 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
(This article belongs to the Special Issue Molecular System Bioenergetics)
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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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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.

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