English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Essential role of accessory subunit LYRM6 in the mechanism of mitochondrial complex I

MPS-Authors
/persons/resource/persons137828

Parey,  Kristian
Medical School, Institute of Biochemistry II, Structural Bioenergetics Group, Goethe University, Frankfurt am Main, Germany;
Centre for Biomolecular Magnetic Resonance, Institute for Biophysical Chemistry, Goethe University, Frankfurt am Main, Germany;
Department of Structural Biology, Max Planck Institute of Biophysics, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Galemou Yoga, E., Parey, K., Djurabekova, A., Haapanen, O., Siegmund, K., Zwicker, K., et al. (2020). Essential role of accessory subunit LYRM6 in the mechanism of mitochondrial complex I. Nature Communications, 11: 6008. doi:10.1038/s41467-020-19778-7.


Cite as: http://hdl.handle.net/21.11116/0000-0007-7A7C-6
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 (β1-β2S2 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.