AUTHOR=Galemou Yoga Etienne , Schiller Jonathan , Zickermann Volker TITLE=Ubiquinone Binding and Reduction by Complex I—Open Questions and Mechanistic Implications JOURNAL=Frontiers in Chemistry VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.672851 DOI=10.3389/fchem.2021.672851 ISSN=2296-2646 ABSTRACT=

NADH: ubiquinone oxidoreductase (complex I) is the first enzyme complex of the respiratory chain. Complex I is a redox-driven proton pump that contributes to the proton motive force that drives ATP synthase. The structure of complex I has been analyzed by x-ray crystallography and electron cryo-microscopy and is now well-described. The ubiquinone (Q) reduction site of complex I is buried in the peripheral arm and a tunnel-like structure is thought to provide access for the hydrophobic substrate from the membrane. Several intermediate binding positions for Q in the tunnel were identified in molecular simulations. Structural data showed the binding of native Q molecules and short chain analogs and inhibitors in the access pathway and in the Q reduction site, respectively. We here review the current knowledge on the interaction of complex I with Q and discuss recent hypothetical models for the coupling mechanism.