Control and regulation of integrated mitochondrial function in metabolic and transport networks.
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 Ca(2+) 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 Ca(2+) dynamics. The calculation also analyzed the control of the concentrations of key regulatory ions and metabolites (Ca(2+), NADH, ADP). The approach we have used demonstrates how properties of integrated systems may be understood through applications of computational modeling and control analysis.
Cortassa
Sonia
S
Johns Hopkins University, School of Medicine, Division of Cardiology 720 Rutland Ave, 1059 Ross Bldg, Baltimore, MD 21205, USA.
O'Rourke
Brian
B
Johns Hopkins University, School of Medicine, Division of Cardiology 720 Rutland Ave, 1059 Ross Bldg, Baltimore, MD 21205, USA.
Winslow
Raimond L
RL
Institute for Computational Medicine, 3400 N. Charles St. CSEB 315, Baltimore, MD 21218, USA.
Aon
Miguel A
MA
Johns Hopkins University, School of Medicine, Division of Cardiology 720 Rutland Ave, 1059 Ross Bldg, Baltimore, MD 21205, USA.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002952:Citric Acid Cycle; D004734:Energy Metabolism; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D010085:Oxidative Phosphorylation
D009243:NAD; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium