Parey 2021 Sci Adv

Parey K, Lasham J, Mills DJ, Djurabekova A, Haapanen O, Yoga EG, Xie H, Kühlbrandt W, Sharma V, Vonck J, Zickermann V (2021) High-resolution structure and dynamics of mitochondrial complex I-Insights into the proton pumping mechanism. https://doi.org/10.1126/sciadv.abj3221

» Sci Adv 7:eabj3221. PMID: 34767441 Open Access

Parey Kristian, Lasham Jonathan, Mills Deryck J, Djurabekova Amina, Haapanen Outi, Galemou Yoga Etienne, Xie Hao, Kuehlbrandt Werner, Sharma Vivek, Vonck Janet, Zickermann Volker (2021) Sci Adv

Abstract: Mitochondrial NADH:ubiquinone oxidoreductase (complex I) is a 1-MDa membrane protein complex with a central role in energy metabolism. Redox-driven proton translocation by complex I contributes substantially to the proton motive force that drives ATP synthase. Several structures of complex I from bacteria and mitochondria have been determined, but its catalytic mechanism has remained controversial. We here present the cryo-EM structure of complex I from Yarrowia lipolytica at 2.1-Å resolution, which reveals the positions of more than 1600 protein-bound water molecules, of which ~100 are located in putative proton translocation pathways. Another structure of the same complex under steady-state activity conditions at 3.4-Å resolution indicates conformational transitions that we associate with proton injection into the central hydrophilic axis. By combining high-resolution structural data with site-directed mutagenesis and large-scale molecular dynamic simulations, we define details of the proton translocation pathways and offer insights into the redox-coupled proton pumping mechanism of complex I.

• Bioblast editor: Plangger M

Labels: MiParea: mt-Structure;fission;fusion 

Enzyme: Complex I