title: Analysis of functional consequences of haplogroup J polymorphisms m.4216T>C and m.3866T>C in human MT-ND1: mutagenesis of homologous positions in Escherichia coli.
abstract: MtDNA sequence variation is presumed to be neutral in effect, but associations with diseases and mtDNA haplogroups have been reported. The aim here was to evaluate the functional consequences of m.4216T>C present in haplogroup J. Furthermore, we evaluated m.3866T>C in MT-ND1, a variant detected in a child belonging to haplogroup J and with an isolated complex I deficiency. Homologous substitutions were introduced into Escherichia coli. NADH dehydrogenase domain activity of NDH-1 with either one or both mutations was markedly decreased suggesting that m.4216T>C and m.3866T>C may have an effect on the structural integrity of complex I.
authors.affiliation: Department of Clinical Medicine, Neurology, University of Oulu, 90014 Oulu, Finland. reetta.hinttala@oulu.fi
authors.forename: Reetta
authors.initials: R
authors.lastname: Hinttala
authors.forename: Marko
authors.initials: M
authors.lastname: Kervinen
authors.forename: Johanna
authors.initials: J
authors.lastname: Uusimaa
authors.forename: Pilvi
authors.initials: P
authors.lastname: Maliniemi
authors.forename: Saara
authors.initials: S
authors.lastname: Finnilä
authors.forename: Heikki
authors.initials: H
authors.lastname: Rantala
authors.forename: Anne M
authors.initials: AM
authors.lastname: Remes
authors.forename: Ilmo E
authors.initials: IE
authors.lastname: Hassinen
authors.forename: Kari
authors.initials: K
authors.lastname: Majamaa
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics* / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis; D009245:NADH Dehydrogenase / Q000235:genetics*; D017354:Point Mutation
chemical_list: D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I; D029968:Escherichia coli Proteins; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human