Thermodynamic efficiency, reversibility, and degree of coupling in energy conservation by the mitochondrial respiratory chain

Mårten Wikström,Roger Springett

doi:10.1038/s42003-020-01192-w

Mårten Wikström, Roger Springett

Open Access

https://doi.org/10.1038/s42003-020-01192-w

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Abstract

The protonmotive mitochondrial respiratory chain, comprising complexes I, III and IV, transduces free energy of the electron transfer reactions to an electrochemical proton gradient across the inner mitochondrial membrane. This gradient is used to drive synthesis of ATP and ion and metabolite transport. The efficiency of energy conversion is of interest from a physiological point of view, since the energy transduction mechanisms differ fundamentally between the three complexes. Here, we have chosen actively phosphorylating mitochondria as the focus of analysis. For all three complexes we find that the thermodynamic efficiency is about 80–90% and that the degree of coupling between the redox and proton translocation reactions is very high during active ATP synthesis. However, when net ATP synthesis stops at a high ATP/ADP.Pi ratio, and mitochondria reach “State 4” with an elevated proton gradient, the degree of coupling drops substantially. The mechanistic cause and the physiological implications of this effect are discussed.

Highlights

The protonmotive mitochondrial respiratory chain, comprising complexes I, III and IV, transduces free energy of the electron transfer reactions to an electrochemical proton gradient across the inner mitochondrial membrane
When the rate of respiration falls to a resting steadystate level due to a high ATP/ADP.Pi ratio (State 4), the degree of coupling is significantly lowered and free energy is dissipated as an increase in entropy
Since thermodynamic efficiency is the product of the flux and force ratios of the output (H+ translocation) versus input reactions (η = −jx; Eq (5)), the flux ratio (j), which equals the H+/e− ratio, is an essential parameter for such an assessment

Summary

Introduction

The protonmotive mitochondrial respiratory chain, comprising complexes I, III and IV, transduces free energy of the electron transfer reactions to an electrochemical proton gradient across the inner mitochondrial membrane. This gradient is used to drive synthesis of ATP and ion and metabolite transport. When the rate of respiration falls to a resting steadystate level due to a high ATP/ADP.Pi ratio (State 4), the degree of coupling is significantly lowered and free energy is dissipated as an increase in entropy This has been ascribed to a proton leak across the inner mitochondrial membrane[7,8,9,10], and/or to mechanistic “slipping” in the proton pumps themselves[11,12,13]. We find that the reduced degree of coupling in State 4 is not uniform among the three respiratory complexes, which suggests control at the mechanistic level of proton pumping

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Results

Conclusion