The nuclear-encoded human NADH : ubiquinone oxidoreductase NDUFA8 subunit:cDNA cloning, chromosomal localization, tissue distribution, and mutation detection in complex-I-deficient patients

We report the cloning of the cDNA sequence of the nuclear-encoded NDUFA8 su bunit of NADH: ubiquinone oxidoreductase, the first mitochondrial respirato ry chain complex. The NDUFA8 open reading frame (ORF) includes 519 bp and e ncodes 172 amino acids (Mr=20.1 kDa). The human cDNA sequence shows 86.2% i dentity with the bovine sequence, whereas the human NDUFA8 amino acid seque nce is 87.8% similar to its bovine PGIV protein counterpart. Both human and bovine NDUFA8 contain a conserved cysteine motif. Polymerase chain reactio n analysis of rodent/human somatic cell hybrids maps the human NDUFA8 gene to chromosome 9. A multiple tissue blot has revealed the highest NDUFA8 mRN A expression in human heart, skeletal muscle, and fetal heart. Mutation ana lysis of the NDUFA8 fibroblast cDNA in 20 patients with an isolated enzymat ic complex I deficiency in cultured skin fibroblasts has revealed two polym orphisms, one within the ORF and the other in the 3' untranslated region of the NDUFA8 cDNA sequence. The allelic frequency of both polymorphisms was similar in controls and complex-I-deficient patients.