Shuttle-mediated proton pumping across the inner mitochondrial membrane

TL;DR

This paper introduces a nanoelectromechanical model explaining how electron-driven proton pumping occurs in mitochondria, highlighting the electrostatic interactions and temperature dependence of the process.

Contribution

The study presents a novel physical model of mitochondrial proton pumping, emphasizing electrostatic interactions and the bidirectional pumping capability.

Findings

Proton gradient generation via electrostatic interaction between electrons and protons.

System can operate as both proton and electron pump depending on conditions.

Uphill proton current peaks near human body temperature (~37°C).

Abstract

Shuttle-assisted charge transfer is pivotal for the efficient energy transduction from the food-stuff electrons to protons in the respiratory chain of animal cells and bacteria. The respiratory chain consists of four metalloprotein Complexes (I-IV) embedded in the inner membrane of a mitochondrion. Three of these complexes pump protons across the membrane, fuelled by the energy of food-stuff electrons. Despite extensive biochemical and biophysical studies, the physical mechanism of this proton pumping is still not well understood. Here we present a nanoelectromechanical model of the electron-driven proton pump related to the second loop of the respiratory chain, where a lipid-soluble ubiquinone molecule shuttles between the Complex I and Complex III, carrying two electrons and two protons. We show that the energy of electrons can be converted to the transmembrane proton potential gradient via the electrostatic interaction between electrons and protons on the shuttle. We find that the system can operate either as a proton pump, or, in the reverse regime, as an electron pump. For membranes with various viscosities, we demonstrate that the uphill proton current peaks near the body temperature $T \approx 37 ^{\circ}$C.