Reverse Electron Transfer by Respiratory Complex I Catalyzed in a Modular Proteoliposome System.
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Publication Date
2022-04-20Journal Title
J Am Chem Soc
ISSN
0002-7863
Publisher
American Chemical Society (ACS)
Volume
144
Issue
15
Pages
6791-6801
Language
eng
Type
Article
This Version
VoR
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Wright, J. J., Biner, O., Chung, I., Burger, N., Bridges, H. R., & Hirst, J. (2022). Reverse Electron Transfer by Respiratory Complex I Catalyzed in a Modular Proteoliposome System.. J Am Chem Soc, 144 (15), 6791-6801. https://doi.org/10.1021/jacs.2c00274
Abstract
Respiratory complex I is an essential metabolic enzyme that uses the energy from NADH oxidation and ubiquinone reduction to translocate protons across an energy transducing membrane and generate the proton motive force for ATP synthesis. Under specific conditions, complex I can also catalyze the reverse reaction, Δp-linked oxidation of ubiquinol to reduce NAD+ (or O2), known as reverse electron transfer (RET). Oxidative damage by reactive oxygen species generated during RET underpins ischemia reperfusion injury, but as RET relies on several converging metabolic pathways, little is known about its mechanism or regulation. Here, we demonstrate Δp-linked RET through complex I in a synthetic proteoliposome system for the first time, enabling complete kinetic characterization of RET catalysis. We further establish the capability of our system by showing how RET in the mammalian enzyme is regulated by the active-deactive transition and by evaluating RET by complex I from several species in which direct assessment has not been otherwise possible. We thus provide new insights into the reversibility of complex I catalysis, an important but little understood mechanistic and physiological feature.
Keywords
Animals, Mammals, Electron Transport Complex I, NAD, Electron Transport, Oxidation-Reduction, Catalysis, Electrons
Sponsorship
Medical Research Council (MC_UU_00015/7)
MRC (MC_UU_00015/2)
Identifiers
35380814, PMC9026280
External DOI: https://doi.org/10.1021/jacs.2c00274
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336909
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