Figure 1.
Illustration of the Components Included in the Model of Mitochondrial Oxidative Phosphorylation
(A) The major components of the electron transport system, which transfers reducing potential from NADH to oxygen, and the F1F0 ATPase, which transduces energy from proton motive force to ATP, are illustrated. Complexes I, III, and IV are labeled C1, C3, and C4, respectively.
(B) The substrate transport process included in the model is shown, including the ANT and PiHt on the inner membrane, and passive permeation of ATP, ADP, AMP, and phosphate across the outer membrane. The AK reaction in the IM space is shown.
(C) Transporters for hydrogen and potassium ions on the inner membrane, including K+/H+ antiporter and passive proton and potassium fluxes, are included. It is assumed that these cations rapidly equilibrate across the outer membrane.
Table 1.
Mitochondrial Model Parameter Values
Table 2.
Standard Free Energies of Respiratory Chain Reactions
Figure 2.
Comparison of Model Simulations to Experimental Data on NADH, MVO2, Cytochrome C Redox, and Matrix pH for Model without Phosphate Control
(A) Results for normalized matrix NADH as a function of buffer inorganic phosphate concentration are shown for the two experimental cases of resting mitochondria ([ADP]e = 0, state 4) and active state mitochondria ([ADP]e = 1.3 mM, state 3).
(B) Results for MVO2 (rate of oxygen consumption) are shown for the same experimental cases as in (A). Experimental data are not available for the resting state, in which a minimal flux through the electron transport system is maintained to compensate for cation flux across the inner membrane.
(C) Results for cytochrome C reduced fraction are shown for the experimental cases as in (A). The black curves correspond to the model equations developed in the text. The red curves correspond to the best-fit model simulations obtained with equation 9 modified to not include the factor [cytC(red)2+]/cytCtot multiplying the expression for JC4.
(D) Matrix pH (model-simulated and experimentally measured) is plotted as a function of buffer phosphate for the experimental cases as in (A).
All computed results in this figure correspond to steady-state simulations of model described under “Mitochondrial Model without Phosphate Control.” Model simulations for [ADP]e = 1.3 mM, and [ADP]e = 0 mM are plotted as solid lines and dashed lines, respectively. Experimental data (circles and triangles) are obtained from [10].
Figure 3.
Comparison of Model Simulations to Experimental Data on Membrane Potential for Model without Phosphate Control
The model without phosphate control is not able to fit the experimental data on mitochondrial membrane potential. Computed results in this figure correspond to steady-state simulations of the model described under “Mitochondrial Model without Phosphate Control.” Model simulations for [ADP]e = 1.3 mM, and [ADP]e = 0 mM are plotted as solid lines and dashed lines, respectively. Experimental data (circles and triangles) are obtained from [10].
Figure 4.
Comparison of Model Simulations to Experimental Data on NADH, MVO2, Cytochrome C Redox, and Matrix pH for Model with Phosphate Control
(A) Results for normalized matrix NADH as a function of buffer inorganic phosphate concentration are shown for the two experimental cases of resting mitochondria ([ADP]e = 0, state 4) and active state mitochondria ([ADP]e = 1.3 mM, state 3).
(B) Results for MVO2 (rate of oxygen consumption) are shown for the same experimental cases as in (A).
(C) Results for cytochrome C reduced fraction are shown for the experimental cases as in (A).
(D) Matrix pH (model-simulated and experimentally measured) is plotted as a function of buffer phosphate for the experimental cases as in (A).
All computed results in this figure correspond to steady-state simulations of the model described under “Mitochondrial Model with Phosphate Control.” Model simulations for [ADP]e = 1.3 mM and [ADP]e = 0 mM are plotted as solid lines and dashed lines, respectively; experimental data are the same as plotted in Figure 2.
Figure 5.
Comparison of Model Simulations to Experimental Data on Membrane Potential for Model with Phosphate Control
The model with phosphate control compares much more favorably to the experimental measurements than the model without phosphate control (see Figure 3). Computed results in this figure correspond to steady-state simulations of the model described under “Mitochondrial Model with Phosphate Control.” Model simulations for [ADP]e = 1.3 mM and [ADP]e = 0 mM are plotted as solid lines and dashed lines, respectively; experimental data are the same as plotted in Figure 3.
Figure 6.
Behavior of Model at Low Oxygen Concentration
Predicted rate of oxygen consumption (MVO2) normalized to maximal rate of oxygen consumption and fraction of cytochome c reduced are plotted against oxygen concentration, which is expressed in micromoles (lower axis) and oxygen partial pressure (upper axis). The oxygen consumption curve was computed for state-3 respiration, corresponding to experimental conditions reported in [18] and [19]. The cytochrome c curve corresponds to state-4 experimental conditions reported in [17]. Inset shows predicted curves for oxygen concentrations from 0 to 5 μM.