Contribution of the Collective Excitations to the Coupled Proton and Energy Transport along Mitochondrial Cristae Membrane in Oxidative Phosphorylation System

Abstract

The results of many experimental and theoretical works indicate that after transport of protons across the mitochondrial inner membrane (MIM) in the oxidative phosphorylation (OXPHOS) system, they are retained on the membrane–water interface in nonequilibrium state with free energy excess due to low proton surface-to-bulk release. This well-established phenomenon suggests that proton trapping on the membrane interface ensures vectorial lateral transport of protons from proton pumps to ATP synthases (proton acceptors). Despite the key role of the proton transport in bioenergetics, the molecular mechanism of proton transfer in the OXPHOS system is not yet completely established. Here, we developed a dynamics model of long-range transport of energized protons along the MIM accompanied by collective excitation of localized waves propagating on the membrane surface. Our model is based on the new data on the macromolecular organization of the OXPHOS system showing the well-ordered structure of respirasomes and ATP synthases on the cristae membrane folds. We developed a two-component dynamics model of the proton transport considering two coupled subsystems: the ordered hydrogen bond (HB) chain of water molecules and lipid headgroups of MIM. We analytically obtained a two-component soliton solution in this model, which describes the motion of the proton kink, corresponding to successive proton hops in the HB chain, and coherent motion of a compression soliton in the chain of lipid headgroups. The local deformation in a soliton range facilitates proton jumps due to water molecules approaching each other in the HB chain. We suggested that the proton-conducting structures formed along the cristae membrane surface promote direct lateral proton transfer in the OXPHOS system. Collective excitations at the water–membrane interface in a form of two-component soliton ensure the coupled non-dissipative transport of charge carriers and elastic energy of MIM deformation to ATP synthases that may be utilized in ATP synthesis providing maximal efficiency in mitochondrial bioenergetics.

The Structure of the Cardiac Mitochondria Respirasome Is Adapted for the β-Oxidation of Fatty Acids

“…Nesterov et al (2022Nesterov et al ( , 2023) developed a dynamic model of the long-range transport of energized protons along the mitochondrial inner membrane accompanied by the collective excitation of localized waves propagating on the membrane surface. This model is based on the new data on the macromolecular organization of the oxidative phosphorylation system (OXPHOS), showing the well-ordered structure of respirasomes and ATP synthases on the cristae membrane folds (Figure 4) [20,21]. The cluster of components of the OXPHOS system at the bends of the cristae of heart mitochondria.…”

“…The area of increased curvature of the membrane is enriched with CL molecules. The figure was adapted from [21]. A schematic model of organizing respiratory chain supercomplexes into a respirasome and then to the respiratory string.…”

“…The area of increased curvature of the membrane is enriched with CL molecules. The figure was adapted from [21].…”

“…( 5) Two enzyme complexes responsible for the β-oxidation of fatty acids are physically attached to the respirasome [29]. Since the electron-transporting complexes that constitute the respirasome's supercomplexes are tightly packed [19][20][21], physical contact with the beta-oxidation enzymes will promote the membrane's reduction/oxidation cycle of the ubiquinone pool.…”

“…For the last 20 years, after discovering the respirasome's structure, many researchers have studied various aspects of the respirasome structure and function [18][19][20][21][22][23][24][25][26][27]. Unfortunately, most of these studies were based on old paradigms.…”