title: Mitochondrial complex I plays an essential role in human respirasome assembly.
abstract: The biogenesis and function of the mitochondrial respiratory chain (RC) involve the organization of RC enzyme complexes in supercomplexes or respirasomes through an unknown biosynthetic process. This leads to structural interdependences between RC complexes, which are highly relevant from biological and biomedical perspectives, because RC defects often lead to severe neuromuscular disorders. We show that in human cells, respirasome biogenesis involves a complex I assembly intermediate acting as a scaffold for the combined incorporation of complexes III and IV subunits, rather than originating from the association of preassembled individual holoenzymes. The process ends with the incorporation of complex I NADH dehydrogenase catalytic module, which leads to the respirasome activation. While complexes III and IV assemble either as free holoenzymes or by incorporation of free subunits into supercomplexes, the respirasomes constitute the structural units where complex I is assembled and activated, thus explaining the significance of the respirasomes for RC function.
authors.affiliation: Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid 28041, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Moreno-Lastres
authors.forename: Flavia
authors.initials: F
authors.lastname: Fontanesi
authors.forename: Inés
authors.initials: I
authors.lastname: García-Consuegra
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martín
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.forename: Antoni
authors.initials: A
authors.lastname: Barrientos
authors.forename: Cristina
authors.initials: C
authors.lastname: Ugalde
mesh_terms: D045744:Cell Line, Tumor; D004579:Electron Transport / Q000502:physiology; D042967:Electron Transport Complex I / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D009097:Multienzyme Complexes; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I