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, wi th Leigh (-like) disease as the main contributor. Enzyme complex activity m easurement in skeletal muscle is the mainstay of the diagnostic process. Fi broblast studies are a prerequisite whenever prenatal enzyme diagnosis is c onsidered. Mitochondrial DNA mutations are found in approximately 5-10% of all complex I deficiencies. Recently, all structural nuclear complex I gene s have been determined at the cDNA level and several at the gDNA level. A c omprehensive 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.