Inborn errors of complex II--unusual human mitochondrial diseases.
The succinate dehydrogenase consists of only four subunits, all nuclearly encoded, and is part of both the respiratory chain and the Krebs cycle. Mutations in the four genes encoding the subunits of the mitochondrial respiratory chain succinate dehydrogenase have been recently reported in human and shown to be associated with a wide spectrum of clinical presentations. Although a comparatively rare deficiency in human, molecularly defined succinate dehydrogenase deficiency has already been found to cause encephalomyopathy in childhood, optic atrophy or tumor in adulthood. Because none of the typical housekeeping genes encoding this respiratory chain complex is known to present tissue-specific isoforms, the tissue-specific involvement represents a quite intriguing question, which is mostly addressed in this review. A differential impairment of electron flow through the respiratory chain, handling of oxygen, and/or metabolic blockade possibly associated with defects in the different subunits that can be advocated to account for tissue-specific involvement is discussed.
Rustin
Pierre
P
Unité de Recherches sur les Handicaps Génétiques de l'Enfant (INSERM U-393), Tour Lavoisier, Hôpital Necker-Enfants Malades, 149, rue de Sèvres, F-75743 Cedex 15, Paris, France. rustin@necker.fr
Rötig
Agnès
A
D002952:Citric Acid Cycle; D042963:Electron Transport Complex II; D005420:Flavoproteins / Q000235:genetics; D005650:Fumarates / Q000378:metabolism; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics; D028361:Mitochondrial Diseases / Q000201:enzymology* / Q000235:genetics; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D009154:Mutation; D010088:Oxidoreductases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D019802:Succinic Acid / Q000378:metabolism
D005420:Flavoproteins; D005650:Fumarates; D009097:Multienzyme Complexes; C032005:fumaric acid; D019802:Succinic Acid; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase