High-resolution cryo-EM structures of respiratory complex I: Mechanism, assembly, and disease

Respiratory complex I is a redox-driven proton pump, accounting for a large part of the electrochemical gradient that powers mitochondrial adenosine triphosphate synthesis. Complex I dysfunction is associated with severe
Respiratory complex I is a redox-driven proton pump, accounting for a large part of the electrochemical gradient that powers mitochondrial adenosine triphosphate synthesis. Complex I dysfunction is associated with severe human diseases. Assembly of the one-megadalton complex I in the inner mitochondrial membrane requires assembly factors and chaperones. We have determined the structure of complex I from the aerobic yeast Yarrowia lipolytica by electron cryo-microscopy at 3.2-Å resolution. A ubiquinone molecule was identified in the access path to the active site. The electron cryo-microscopy structure indicated an unusual lipid-protein arrangement at the junction of membrane and matrix arms that was confirmed by molecular simulations. The structure of a complex I mutant and an assembly intermediate provide detailed molecular insights into the cause of a hereditary complex I-linked disease and complex I assembly in the inner mitochondrial membrane.
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Metadaten
Author:Kristian Kurt Parey, Outi Haapanen, Vivek Sharma, Harald Köfeler, Thomas Züllig, Simone Prinz, Karin Siegmund, Ilka Wittig, Deryck J. Mills, Janet Vonck, Werner Kühlbrandt, Volker Zickermann
URN:urn:nbn:de:hebis:30:3-543232
DOI:http://dx.doi.org/10.1126/sciadv.aax9484
ISSN:2375-2548
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=31844670
Parent Title (English):Science advances
Publisher:Assoc.
Place of publication:Washington, DC [u. a.]
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/12/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/06/17
Volume:5
Issue:12, eaax9484
Pagenumber:11
First Page:1
Last Page:10
Note:
Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
HeBIS PPN:467349940
Institutes:Biochemie und Chemie
Biowissenschaften
Medizin
Sonderforschungsbereiche / Forschungskollegs
MPI für Biophysik
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0

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