title: Human NADH:ubiquinone oxidoreductase.
abstract: NADH:ubiquinone oxidoreductase consists of at least 43 proteins; seven are encoded by the mitochondrial genome, while the remainder are encoded by the nuclear genome. A deficient activity of this enzyme complex is frequently observed in the clinical heterogeneous group of mitochondrial disorders, with Leigh (-like) disease as the main contributor. Enzyme complex activity measurement in skeletal muscle is the mainstay of the diagnostic process. Fibroblast studies are a prerequisite whenever prenatal enzyme diagnosis is considered. Mitochondrial DNA mutations are found in approximately 5-10% of all complex I deficiencies. Recently, all structural nuclear complex I genes have been determined at the cDNA level and several at the gDNA level. A comprehensive mutational analysis study of all complex I nuclear genes in a group of 20 patients exhibiting this deficiency revealed mutations in about 40%. Here, we describe the enzymic methods we use and the recent progress made in genomics and cell biology of human complex I.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, University Medical Center Nijmegen, The Netherlands. J.Smeitink@ckskg.azn.nl
authors.forename: J
authors.initials: J
authors.lastname: Smeitink
authors.forename: R
authors.initials: R
authors.lastname: Sengers
authors.forename: F
authors.initials: F
authors.lastname: Trijbels
authors.forename: L
authors.initials: L
authors.lastname: van den Heuvel
mesh_terms: D002824:Chorionic Villi / Q000201:enzymology; D042967:Electron Transport Complex I; D023281:Genomics; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000235:genetics; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D010085:Oxidative Phosphorylation; D012867:Skin / Q000201:enzymology
chemical_list: D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I