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.
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.
Hinttala
Reetta
R
Department of Clinical Medicine, Neurology, University of Oulu, 90014 Oulu, Finland. reetta.hinttala@oulu.fi
Kervinen
Marko
M
Uusimaa
Johanna
J
Maliniemi
Pilvi
P
Finnilä
Saara
S
Rantala
Heikki
H
Remes
Anne M
AM
Hassinen
Ilmo E
IE
Majamaa
Kari
K
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
D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I; D029968:Escherichia coli Proteins; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human