title: Accessory subunit NUYM (NDUFS4) is required for stability of the electron input module and activity of mitochondrial complex I.
abstract: Mitochondrial complex I is an intricate 1MDa membrane protein complex with a central role in aerobic energy metabolism. The minimal form of complex I consists of fourteen central subunits that are conserved from bacteria to man. In addition, eukaryotic complex I comprises some 30 accessory subunits of largely unknown function. The gene for the accessory NDUFS4 subunit of human complex I is a hot spot for fatal pathogenic mutations in humans. We have deleted the gene for the orthologous NUYM subunit in the aerobic yeast Yarrowia lipolytica, an established model system to study eukaryotic complex I and complex I linked diseases. We observed assembly of complex I which lacked only subunit NUYM and retained weak interaction with assembly factor N7BML (human NDUFAF2). Absence of NUYM caused distortion of iron sulfur clusters of the electron input domain leading to decreased complex I activity and increased release of reactive oxygen species. We conclude that NUYM has an important stabilizing function for the electron input module of complex I and is essential for proper complex I function.
authors.affiliation: Structural Bioenergetics Group, Institute of Biochemistry II, Medical School, Goethe-University Frankfurt am Main, Germany.
authors.forename: Flora
authors.initials: F
authors.lastname: Kahlhöfer
authors.affiliation: Structural Bioenergetics Group, Institute of Biochemistry II, Medical School, Goethe-University Frankfurt am Main, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kmita
authors.affiliation: Functional Proteomics, Institute of Biochemistry I, Medical School, Goethe-University Frankfurt am Main, Germany; Cluster of Excellence Frankfurt "Macromolecular Complexes", Goethe-University Frankfurt am Main, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Wittig
authors.affiliation: Institute of Biochemistry I, Medical School, Goethe University Frankfurt am Main, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Zwicker
authors.affiliation: Structural Bioenergetics Group, Institute of Biochemistry II, Medical School, Goethe-University Frankfurt am Main, Germany; Cluster of Excellence Frankfurt "Macromolecular Complexes", Goethe-University Frankfurt am Main, Germany. Electronic address: Zickermann@med.uni-frankfurt.de.
authors.forename: Volker
authors.initials: V
authors.lastname: Zickermann
mesh_terms: D042967:Electron Transport Complex I / Q000378:metabolism*; D004583:Electrons; D004734:Energy Metabolism / Q000502:physiology; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D025062:Yarrowia / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I
keywords: Complex I assembly; Iron sulfur cluster; N7BML; NADH:ubiquinone oxidoreductase; NDUFAF2; ROS