Control over the contribution of the mitochondrial membrane potential (DeltaPsi) and proton gradient (DeltapH) to the protonmotive force (Deltap). In silico studies

Abstract

The protonmotive force across the inner mitochondrial membrane (Deltap) has two components: membrane potential (DeltaPsi) and the gradient of proton concentration (DeltapH). The computer model of oxidative phosphorylation developed previously by Korzeniewski et al. (Korzeniewski, B., Noma, A., and Matsuoka, S. (2005) Biophys. Chem. 116, 145-157) was modified by including the K+ uniport, K+/H+ exchange across the inner mitochondrial membrane, and membrane capacitance to replace the fixed DeltaPsi/DeltapH ratio used previously with a variable one determined mechanistically. The extended model gave good agreement with experimental results. Computer simulations showed that the contribution of DeltaPsi and DeltapH to Deltap is determined by the ratio of the rate constants of the K+ uniport and K+/H+ exchange and not by the absolute values of these constants. The value of Deltap is mostly controlled by ATP usage. The metabolic control over the DeltaPsi/DeltapH ratio is exerted mostly by K+ uniport and K+/H+ exchange in the presence of these processes, and by the ATP usage, ATP/ADP carrier, and phosphate carrier in the absence of them. The K+ circulation across the inner mitochondrial membrane is controlled mainly by K+ uniport and K+/H+ exchange, whereas H+ circulation by ATP usage. It is demonstrated that the secondary K+ ion transport is not necessary for maintaining the physiological DeltaPsi/DeltapH ratio.

FIGURE 1.

Scheme of the oxidative phosphorylation system. The elements of the system taken into account explicitly within the model of oxidative phosphorylation used in the present study are presented. C_m, membrane capacitance; ΔΨ, membrane potential.

FIGURE 2.

Simulated dependence of Δp, ΔΨ, ΔpH, and [K⁺]_i on the rate constant of K⁺ uniport (k_Kuni) and K⁺/H⁺ exchange (k_KHex). A, dependence on k_Kuni; B, dependence on k_KHex; C, dependence on k_Kuni and k_KHex at the fixed k_Kuni/k_KHex ratio equal to 2.896·10^-3.

FIGURE 3.

Simulated dependence of Δp, ΔΨ, and ΔpH on extramitochondrial [ADP] (A), [ATP] (B), [P_i] (C), and [K⁺] (D). Thick lines without points, computer simulations; points connected with thin lines, experimental data; solid lines, Δp; dotted lines, ΔΨ; dashed lines, ΔpH; full symbols in C, data from Ref. ; empty symbols in C, data from Ref. ; empty symbols in D, data from Ref. .

FIGURE 4.

Simulated dependence of the reduction level of cytochrome c on extramitochondrial [P_i].

FIGURE 5.

Simulated control coefficients of particular components of the system over Δp.

FIGURE 6.

Simulated control coefficients of particular components of the system over u = ΔΨ/Δp. A, in the presence of K⁺ uniport and K⁺/H⁺ exchange; B, in the absence of K⁺ uniport and K⁺/H⁺ exchange.

FIGURE 7.

Simulated control coefficients of particular components of the system over the K⁺ circulation flux.