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.