control and regulation of integrated mitochondrial function in metabolic and transport networks控制和调节代谢和运输网络的集成线粒体功能.pdf

Int. J. Mol. Sci. 2009, 10, 1500-1513; doi:10.3390/ijm OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Review Control and Regulation of Integrated Mitochondrial Function in Metabolic and Transport Networks Sonia Cortassa 1,*, Brian O’Rourke 1, Raimond L. Winslow 2 and Miguel A. Aon 1 1 Johns Hopkins University, School of Medicine, Division of Cardiology 720 Rutland Ave, 1059 Ross Bldg, Baltimore, MD 21205, USA; E-Mails: bor@ (B.O‘R.); maon1@ (M.A.) 2 Institute for Computational Medicine, 3400 N. Charles St. CSEB 315, Baltimore, MD 21218, USA; E-Mail: rwinslow@ (R.W.) * Author to whom correspondence should be addressed; E-Mail: scortas1@; Tel. +1-410-955-2759; Fax: +1-410-502-5055 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