LHON/MELAS overlap mutation in ND1 subunit of mitochondrial complex I affects ubiquinone binding as revealed by modeling in Escherichia coli NDH-1

► ND1 subunit is adjacent to the ubiquinone binding site of complex I. ► Involvement of E. coli NuoH-E36, the homolog of ND1-E24, in quinone binding is shown. ► ND1-E24 lies in the ubiquinone binding domain delineated by PSST and 49 kDa subunits. ► NUOH-E36 mutation effects corroborate the m.3376G > A pathogenicity in LHON/MELAS. ► m.3376G > A combines enzymic consequences of separate LHON and MELAS mutations.