title: Mitochondrial complex I deficiency of nuclear origin I. Structural genes.
abstract: Complex I (or NADH-ubiquinone oxidoreductase), is by far the largest respiratory chain complex with 38 subunits nuclearly encoded and 7 subunits encoded by the mitochondrial genome. Its deficiency is the most frequently encountered in mitochondrial disorders. Here, we summarize recent data obtained on architecture of complex I, and review the pathogenic mutations identified to date in nuclear structural complex I genes. The structural NDUFS1, NDUFS2, NDUFV1, and NDUFS4 genes are mutational hot spot genes for isolated complex I deficiency. The majority of the pathogenic mutations are private and the genotype-phenotype correlation is inconsistent in the rare recurrent mutations.
authors.affiliation: Laboratoire de Biochimie, APHP Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre cedex, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Pagniez-Mammeri
authors.forename: Sandrine
authors.initials: S
authors.lastname: Loublier
authors.forename: Alain
authors.initials: A
authors.lastname: Legrand
authors.forename: Paule
authors.initials: P
authors.lastname: Bénit
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Slama
mesh_terms: D004579:Electron Transport; D042967:Electron Transport Complex I / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D028361:Mitochondrial Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; C487793:NDUFS1 protein, human; C112232:NDUFV1 protein, human; D009687:Nuclear Proteins; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C496411:NDUFS2 protein, human; C427643:NDUFS4 protein, human