Mutations in structural genes of complex I associated with neurological diseases.

Salvatore Scacco, Vittoria Petruzzella, Enrico Bertini, Arcangela Luso, Francesco Papa, Francesco Bellomo, Anna Signorile, Alessandra Torraco, Sergio Papa

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)254-262
Number of pages9
JournalItalian Journal of Biochemistry
Issue number3-4
Publication statusPublished - Sept 2006

ASJC Scopus subject areas

  • Biochemistry


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