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.
Highlights
Respiratory complex I is a very large membrane protein found in the inner mitochondrial membrane and in the plasma membrane of aerobic bacteria (Hirst, 2013; Sazanov, 2015; Galemou Yoga et al, 2020a)
The structure of complex I has been determined by x-ray crystallography (Baradaran et al, 2013; Zickermann et al, 2015) and by electron cryo-microscopy (Fiedorczuk et al, 2016; Zhu et al, 2016; Agip et al, 2019; Parey et al, 2019, 2020; Grba and Hirst, 2020; Kampjut and Sazanov, 2020; Soufari et al, 2020; Klusch et al, 2021)
We have proposed that a concerted rearrangement of loops in subunits NDUFS2, ND1, and ND3 is critical for converting the energy released during Q reduction into pump strokes (Zickermann et al, 2015)
Summary
Respiratory complex I ( known as NADH dehydrogenase or NDH-1) is a very large membrane protein found in the inner mitochondrial membrane and in the plasma membrane of aerobic bacteria (Hirst, 2013; Sazanov, 2015; Galemou Yoga et al, 2020a). Complex I couples electron transfer from NADH to quinone (Q) to the translocation of protons across the bioenergetic membrane. Fourteen complex I subunits are conserved from bacteria to human These so-called central subunits harbor all bioenergetic core functions of the enzyme complex. The NADH oxidation module (N module) and the ubiquinone reduction module (Q module) constitute the PA, whereas the proton pumping module (P module) forms the MA of the enzyme. We focus on the progress in the understanding of Q binding and reduction by complex I and its mechanistic implications
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