Disease relevance of NDUFS7

• We report the first missense mutation within the nuclear encoded complex I subunit, NDUFS7, in 2 siblings with neuropathologically proven complex I-deficient Leigh syndrome [1].

High impact information on NDUFS7

• Nucleotide sequence of a cDNA clone from broccoli with high identity with the PSST subunit of NADH:ubiquinone oxidoreductase [2].
• Iron-sulfur cluster N2 and the PSST and 49 kDa subunits were identified as key players in ubiquinone reduction and proton pumping [3].
• We found significant and conserved sequence differences in the PSST/Nqo6/NuoB, 49kDa/Nqo4/NuoD, and ND1/Nqo8/NuoH subunit homologs between complex I/NDH-1 and [NiFe] hydrogenases [4].
• The cDNA of the PSST protein was used to investigate tissue-specific expression and to localize the gene for this subunit to chromosome 19p13 [5].
• Mutagenesis studies showed that efficient processing of PSST to PSST[1-10] required the RXRXXL motif [6].

Biological context of NDUFS7

• Photoaffinity labeling with the highly potent and specific inhibitor trifluoromethyldiazirinyl-[(3)H]pyridaben ([(3)H]TDP) labels only the PSST and ND1 subunits of complex I in electron transport particles [7].
• Perhaps the common action of MPP(+) and stigmatellin on the functional coupling of the PSST and ND1 subunits is initiated by binding at a semiquinone binding site in complex I [7].
• Leigh mutations in the 49-kDa and PSST homologous subunits are found in regions that are at the boundaries of the ubiquinone-reducing catalytic core [8].
• Three copies of the PSST gene were identified in the lupine genomic root library, however, only two transcripts were found in the lupine root cDNA library [9].

Other interactions of NDUFS7

• While homozygosity for a V122M substitution in NDUFS7 (PSST) has been found in two siblings with neuropathologically proven Leigh syndrome (R. Triepels et al., Ann. Neurol. 45 (1999) 787), heterozygosity for a P79L and a R102H substitution in NDUFS8 (TYKY) has been found in another patient (J. Loeffen et al., Am. J. Hum. Genet. 63 (1998) 1598) [10].

References