Modeling of ATP-ADP steady-state exchange rate mediated by the adenine nucleotide translocase in isolated mitochondria.
A computational model for the ATP-ADP steady-state exchange rate mediated by adenine nucleotide translocase (ANT) versus mitochondrial membrane potential dependence in isolated rat liver mitochondria is presented. The model represents the system of three ordinary differential equations, and the basic components included are ANT, F(0)/F(1)-ATPase, and the phosphate carrier. The model reproduces quantitatively the relationship between mitochondrial membrane potential and the ATP-ADP steady-state exchange rate mediated by the ANT operating in the forward mode, with the assumption that the phosphate carrier functions under rapid equilibrium. Furthermore, the model can simulate the kinetics of experimentally measured data on mitochondrial membrane potential titrated by an uncoupler. Verified predictions imply that the ADP influx rate is highly dependent on the mitochondrial membrane potential, and in the 0-100 mV range it is close to zero, owing to extremely low matrix ATP values. In addition to providing theoretical values of free matrix ATP and ADP, the model explains the diminished ADP-ATP exchange rate in the presence of nigericin, a condition in which there is hyperpolarization of the inner mitochondrial membrane at the expense of the mitochondrial Delta pH gradient; the latter parameter influences matrix inorganic phosphate and ATP concentrations in a manner also described.
Institute for Systems Biology SPb, Moscow, Russia.
Eugeniy
E
Metelkin
Oleg
O
Demin
Zsuzsanna
Z
Kovács
Christos
C
Chinopoulos
D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D007700:Kinetics; D008930:Mitochondria, Liver / Q000201:enzymology* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D009550:Nigericin / Q000378:metabolism; D010101:Oxygen Consumption; D010766:Phosphorylation; D051381:Rats
D024101:Mitochondrial Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D009550:Nigericin