Human NADH:ubiquinone oxidoreductase.
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.
Smeitink
J
J
Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, University Medical Center Nijmegen, The Netherlands. J.Smeitink@ckskg.azn.nl
Sengers
R
R
Trijbels
F
F
van den Heuvel
L
L
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
D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I