title: The oxidative phosphorylation (OXPHOS) system: nuclear genes and human genetic diseases.
abstract: The ubiquitous nature of mitochondria, the dual genetic foundation of the respiratory chain in mitochondrial and nuclear genome, and the peculiar rules of mitochondrial genetics all contribute to the extraordinary heterogeneity of clinical disorders associated with defects of oxidative phosphorylation (mitochondrial encephalomyopathies). Here, we review recent findings about nuclear gene defects in isolated OXPHOS enzyme complex deficiency. This information should help in identifying patients with mitochondrial disease and defining a biochemical and molecular basis of the disorder found in each patient. This knowledge is indispensable for accurate genetic counseling and prenatal diagnosis, and is a prerequisite for the development of rational therapies, which are still, at present, woefully inadequate.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Medical Centre Nijmegen, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: van den Heuvel
authors.forename: J
authors.initials: J
authors.lastname: Smeitink
mesh_terms: D002467:Cell Nucleus / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D014450:Electron Transport Complex III / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000235:genetics; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000235:genetics; D010085:Oxidative Phosphorylation; D006180:Proton-Translocating ATPases / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D006180:Proton-Translocating ATPases; D014450:Electron Transport Complex III