title: Functional implications from an unexpected position of the 49-kDa subunit of NADH:ubiquinone oxidoreductase.
abstract: Membrane-bound complex I (NADH:ubiquinone oxidoreductase) of the respiratory chain is considered the main site of mitochondrial radical formation and plays a major role in many mitochondrial pathologies. Structural information is scarce for complex I, and its molecular mechanism is not known. Recently, the 49-kDa subunit has been identified as part of the "catalytic core" conferring ubiquinone reduction by complex I. We found that the position of the 49-kDa subunit is clearly separated from the membrane part of complex I, suggesting an indirect mechanism of proton translocation. This contradicts all hypothetical mechanisms discussed in the field that link proton translocation directly to redox events and suggests an indirect mechanism of proton pumping by redox-driven conformational energy transfer.
authors.affiliation: Universität Frankfurt, Fachbereich Medizin, Institut für Biochemie I, D-60590 Frankfurt am Main, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Zickermann
authors.forename: Mihnea
authors.initials: M
authors.lastname: Bostina
authors.forename: Carola
authors.initials: C
authors.lastname: Hunte
authors.forename: Teresa
authors.initials: T
authors.lastname: Ruiz
authors.forename: Michael
authors.initials: M
authors.lastname: Radermacher
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D001665:Binding Sites; D042967:Electron Transport Complex I; D004735:Energy Transfer; D018604:Epitope Mapping; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry* / Q000276:immunology / Q000502:physiology*; D010084:Oxidation-Reduction; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry* / Q000276:immunology / Q000502:physiology*; D017494:Proton Pumps / Q000378:metabolism; D017385:Sequence Homology; D025062:Yarrowia / Q000201:enzymology
chemical_list: D000906:Antibodies; D021122:Protein Subunits; D017494:Proton Pumps; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I