Issue 23, 2023

Horizontal proton transfer across the antiporter-like subunits in mitochondrial respiratory complex I

Abstract

Respiratory complex I is a redox-driven proton pump contributing to about 40% of total proton motive force required for mitochondrial ATP generation. Recent high-resolution cryo-EM structural data revealed the positions of several water molecules in the membrane domain of the large enzyme complex. However, it remains unclear how protons flow in the membrane-bound antiporter-like subunits of complex I. Here, we performed multiscale computer simulations on high-resolution structural data to model explicit proton transfer processes in the ND2 subunit of complex I. Our results show protons can travel the entire width of antiporter-like subunits, including at the subunit–subunit interface, parallel to the membrane. We identify a previously unrecognized role of conserved tyrosine residues in catalyzing horizontal proton transfer, and that long-range electrostatic effects assist in reducing energetic barriers of proton transfer dynamics. Results from our simulations warrant a revision in several prevailing proton pumping models of respiratory complex I.

Graphical abstract: Horizontal proton transfer across the antiporter-like subunits in mitochondrial respiratory complex I

Supplementary files

Article information

Article type
Edge Article
Submitted
19 Mar 2023
Accepted
09 May 2023
First published
10 May 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2023,14, 6309-6318

Horizontal proton transfer across the antiporter-like subunits in mitochondrial respiratory complex I

O. Zdorevskyi, A. Djurabekova, J. Lasham and V. Sharma, Chem. Sci., 2023, 14, 6309 DOI: 10.1039/D3SC01427D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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