Effects of pathogenic mutations in membrane subunits of mitochondrial Complex I on redox activity and proton translocation studied by modeling in Escherichia coli.
Effects of Complex I mutations were studied by modeling in NuoH, NuoJ or NuoK subunits of Escherichia coli NDH-1 by simultaneous optical monitoring of deamino-NADH oxidation and proton translocation and fitting to the data a model equation of transmembrane proton transport. A homolog of the ND1-E24 LHON/MELAS mutation caused 95% inhibition of d-NADH oxidation and proton translocation. The NuoJ-Y59F replacement decreased proton translocation. The NuoK-E72Q mutation lowered the enzyme activity, but proton pumping could be rescued by the double mutation NuoK-E72Q/I39D. Moving the NuoK-E72/E36 pair one helix turn towards the periplasm did not affect redox activity but decreased proton pumping.
Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. Electronic address: jukka.patsi@oulu.fi.
Jukka
J
Pätsi
Department of Ophthalmology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. Electronic address: marko.kervinen@fimnet.fi.
Marko
M
Kervinen
Department of Neurology and Medical Research Center, Oulu University Hospital and University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. Electronic address: laura.kytovuori@oulu.fi.
Laura
L
Kytövuori
Department of Neurology and Medical Research Center, Oulu University Hospital and University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. Electronic address: kari.majamaa@oulu.fi.
Kari
K
Majamaa
Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. Electronic address: ilmo.hassinen@oulu.fi.
Ilmo E
IE
Hassinen
D001692:Biological Transport; D042967:Electron Transport Complex I / Q000235:genetics* / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000201:enzymology* / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D010084:Oxidation-Reduction; D011522:Protons
D050505:Mutant Proteins; D011522:Protons; D042967:Electron Transport Complex I
Escherichia coli; Mitochondrial disease; NADH:ubiquinone oxidoreductase; Proton translocation