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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 human diseases. Assembly of the one-megadalton complex I in the inner mitochond...

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Detalles Bibliográficos
Autores principales: Parey, Kristian, Haapanen, Outi, Sharma, Vivek, Köfeler, Harald, Züllig, Thomas, Prinz, Simone, Siegmund, Karin, Wittig, Ilka, Mills, Deryck J., Vonck, Janet, Kühlbrandt, Werner, Zickermann, Volker
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905873/
https://www.ncbi.nlm.nih.gov/pubmed/31844670
http://dx.doi.org/10.1126/sciadv.aax9484
Descripción
Sumario: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.