Schiller 2022 Pharmaceuticals (Basel)

Schiller J, Zickermann V (2022) Binding of natural inhibitors to respiratory complex I. https://doi.org/10.3390/ph15091088

» Pharmaceuticals (Basel) 15:1088. PMID: 36145309 Open Access

Schiller Jonathan, Zickermann Volker (2022) Pharmaceuticals (Basel)

Abstract: NADH:ubiquinone oxidoreductase (respiratory complex I) is a redox-driven proton pump with a central role in mitochondrial oxidative phosphorylation. The ubiquinone reduction site of complex I is located in the matrix arm of this large protein complex and connected to the membrane via a tunnel. A variety of chemically diverse compounds are known to inhibit ubiquinone reduction by complex I. Rotenone, piericidin A, and annonaceous acetogenins are representatives of complex I inhibitors from biological sources. The structure of complex I is determined at high resolution, and inhibitor binding sites are described in detail. In this review, we summarize the state of knowledge of how natural inhibitors bind in the Q reduction site and the Q access pathway and how their inhibitory mechanisms compare with that of a synthetic anti-cancer agent.

• Bioblast editor: Plangger M

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Enzyme: Complex I