Ubiquinone Binding and Reduction by Complex I-Open Questions and Mechanistic Implications

Etienne Galemou Yoga; Jonathan Schiller; Volker Zickermann

doi:10.3389/fchem.2021.672851

Ubiquinone Binding and Reduction by Complex I-Open Questions and Mechanistic Implications

Front Chem. 2021 Apr 30:9:672851. doi: 10.3389/fchem.2021.672851. eCollection 2021.

Authors

Etienne Galemou Yoga^{1

2}, Jonathan Schiller^{1

2}, Volker Zickermann^{1

2}

Affiliations

¹ Institute of Biochemistry II, University Hospital, Goethe University, Frankfurt, Germany.
² Centre for Biomolecular Magnetic Resonance, Institute for Biophysical Chemistry, Goethe University, Frankfurt, Germany.

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.

Keywords: NADH dehydrogenase; electron transfer; inhibitor; oxidative phosphorylation; proton pumping; respiratory chain; semiquinone.

Publication types

Review