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Galemou Yoga 2020 Nat Commun

From Bioblast
Publications in the MiPMap
Galemou Yoga E, Parey K, Djurabekova A, Haapanen O, Siegmund K, Zwicker K, Sharma V, Zickermann V, Angerer H (2020) Essential role of accessory subunit LYRM6 in the mechanism of mitochondrial complex I. https://doi.org/10.1038/s41467-020-19778-7

ยป Nat Commun 11:6008. PMID: 33243981 Open Access

Galemou Yoga Etienne, Parey Kristian, Djurabekova Amina, Haapanen Outi, Siegmund Karin, Zwicker Klaus, Sharma Vivek, Zickermann Volker, Angerer Heike (2020) Nat Commun

Abstract: Respiratory complex I catalyzes electron transfer from NADH to ubiquinone (Q) coupled to vectorial proton translocation across the inner mitochondrial membrane. Despite recent progress in structure determination of this very large membrane protein complex, the coupling mechanism is a matter of ongoing debate and the function of accessory subunits surrounding the canonical core subunits is essentially unknown. Concerted rearrangements within a cluster of conserved loops of central subunits NDUFS2 (ฮฒ1-ฮฒ2S2 loop), ND1 (TMH5-6ND1 loop) and ND3 (TMH1-2ND3 loop) were suggested to be critical for its proton pumping mechanism. Here, we show that stabilization of the TMH1-2ND3 loop by accessory subunit LYRM6 (NDUFA6) is pivotal for energy conversion by mitochondrial complex I. We determined the high-resolution structure of inactive mutant F89ALYRM6 of eukaryotic complex I from the yeast Yarrowia lipolytica and found long-range structural changes affecting the entire loop cluster. In atomistic molecular dynamics simulations of the mutant, we observed conformational transitions in the loop cluster that disrupted a putative pathway for delivery of substrate protons required in Q redox chemistry. Our results elucidate in detail the essential role of accessory subunit LYRM6 for the function of eukaryotic complex I and offer clues on its redox-linked proton pumping mechanism.

โ€ข Bioblast editor: Plangger M


Labels: MiParea: mt-Structure;fission;fusion 



Enzyme: Complex I