title: Respiratory complex I in brain development and genetic disease.
abstract: A study is presented on the expression and activity of complex I, as well as of other complexes of the respiratory chain, in the course of brain development and inherited encephalopathies. Investigations on mouse hippocampal cells show that differentiation of these cells both in vivo and in cell cultures is associated with the expression of a functional complex I, whose activity markedly increases with respect to that of complexes III and IV. Data are presented on genetic defects of complex I in six children with inborn encephalopathy associated with isolated deficiency of the complex. Mutations have been identified in nuclear and mitochondrial genes coding for subunits of the complex. Different mutations were found in the nuclear NDUFS4 gene coding for the 18 kD (IP, AQDQ) subunit of complex I. All the NDUFS4 mutations resulted in impairment of the assembly of a functional complex. The observations presented provide evidence showing a critical role of complex I in differentiation and functional activity of brain cells.
authors.affiliation: Department of Medical Biochemistry and Medical Biology, University of Bari, Piazza G. Cesare 70124 Bari, Italy. papabchm@cimedoc.uniba.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
authors.forename: Vittoria
authors.initials: V
authors.lastname: Petruzzella
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scacco
authors.forename: Rosaria
authors.initials: R
authors.lastname: Vergari
authors.forename: Damiano
authors.initials: D
authors.lastname: Panelli
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tamborra
authors.forename: Patrizia
authors.initials: P
authors.lastname: Corsi
authors.forename: Margherita
authors.initials: M
authors.lastname: Picciariello
authors.forename: Rossana
authors.initials: R
authors.lastname: Lambo
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D051379:Mice; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000201:enzymology
chemical_list: D018076:DNA, Complementary; D042967:Electron Transport Complex I