6rfr

Publication Abstract from PubMed

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-A 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.

High-resolution cryo-EM structures of respiratory complex I: Mechanism, assembly, and disease.,Parey K, Haapanen O, Sharma V, Kofeler H, Zullig T, Prinz S, Siegmund K, Wittig I, Mills DJ, Vonck J, Kuhlbrandt W, Zickermann V Sci Adv. 2019 Dec 11;5(12):eaax9484. doi: 10.1126/sciadv.aax9484. eCollection, 2019 Dec. PMID:31844670^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.