title: Respiratory chain complex I deficiency.
abstract: Oxidative phosphorylation disorders make a contribution of 1 per 10,000 live births in man, of which isolated complex I deficiency is frequently the cause. Complex I, or NADH:ubiquinone oxidoreductase, is the largest multi-protein enzyme complex of the mitochondrial electron transfer chain. In complex I deficiency, various clinical phenotypes have been recognized, often resulting in multi-system disorders with a fatal outcome at a young age. Recent advances in complex I deficiency, regarding clinical, biochemical, and molecular aspects are described. However, the genetic causes of about 60% of complex I deficiency remain unclear. As a consequence, further research will be needed to clarify the genetic defects in the remaining cases. Novel strategies in which interesting non-structural nuclear-encoded disease-causing genes may be found, as well as the molecular genetic composition of human complex I, are presented.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, University Medical Center Nijmegen, The Netherlands.
authors.forename: R H
authors.initials: RH
authors.lastname: Triepels
authors.forename: L P
authors.initials: LP
authors.lastname: Van Den Heuvel
authors.forename: J M
authors.initials: JM
authors.lastname: Trijbels
authors.forename: J A
authors.initials: JA
authors.lastname: Smeitink
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I; D006801:Humans; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D012343:RNA, Transfer / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D012343:RNA, Transfer; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D010100:Oxygen