title: Mutations in structural genes of complex I associated with neurological diseases.
abstract: This paper summarizes observations on the genetic and biochemical basis of hereditary defects of complex I (NADH-ubiquinone oxidoreductase) of the respiratory chain in human neurological patients. Two different types of functional defects of the complex are described. In one type mutations in the NDUFS1 and NDUFS4 nuclear structural genes of the complex were identified in two unrelated families. Both NDUFS1 and NDUFS4 neurological disorders were transmitted by autosomic recessive inheritance. The two mutations resulted in different impact on cellular metabolism. The NDUFS4 mutation, giving a more severe, fatal pathological pattern, resulted in a defective assembly of the complex and complete suppression of the enzymatic activity. The NDUFS1 mutation, with less severe progressive pathology, caused only partial inhibition of the complex but enhanced production of oxygen free radicals. In the second type of deficiencies extensive mutational analysis did not reveal pathogenic mutations in complex I genes but a decline in the level and activity of complex I, III, and IV were found, apparently associated with alteration in the cardiolipin membrane distribution.
authors.affiliation: Department of Medical Biochemistry, Biology and Physics, University of Bari, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scacco
authors.forename: Vittoria
authors.initials: V
authors.lastname: Petruzzella
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Arcangela
authors.initials: A
authors.lastname: Luso
authors.forename: Francesco
authors.initials: F
authors.lastname: Papa
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellomo
authors.forename: Anna
authors.initials: A
authors.lastname: Signorile
authors.forename: Alessandra
authors.initials: A
authors.lastname: Torraco
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
mesh_terms: D000328:Adult; D002648:Child; D042967:Electron Transport Complex I / Q000172:deficiency / Q000235:genetics*; D005260:Female; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D009245:NADH Dehydrogenase / Q000235:genetics; D013481:Superoxides / Q000378:metabolism
chemical_list: C487793:NDUFS1 protein, human; D013481:Superoxides; D006861:Hydrogen Peroxide; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C427643:NDUFS4 protein, human