title: The nuclear-encoded human NADH:ubiquinone oxidoreductase NDUFA8 subunit: cDNA cloning, chromosomal localization, tissue distribution, and mutation detection in complex-I-deficient patients.
abstract: We report the cloning of the cDNA sequence of the nuclear-encoded NDUFA8 subunit of NADH: ubiquinone oxidoreductase, the first mitochondrial respiratory chain complex. The NDUFA8 open reading frame (ORF) includes 519 bp and encodes 172 amino acids (Mr=20.1 kDa). The human cDNA sequence shows 86.2% identity with the bovine sequence, whereas the human NDUFA8 amino acid sequence is 87.8% similar to its bovine PGIV protein counterpart. Both human and bovine NDUFA8 contain a conserved cysteine motif. Polymerase chain reaction analysis of rodent/human somatic cell hybrids maps the human NDUFA8 gene to chromosome 9. A multiple tissue blot has revealed the highest NDUFA8 mRNA expression in human heart, skeletal muscle, and fetal heart. Mutation analysis of the NDUFA8 fibroblast cDNA in 20 patients with an isolated enzymatic complex I deficiency in cultured skin fibroblasts has revealed two polymorphisms, 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.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, University Children's Hospital, Department of Pediatrics, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Triepels
authors.forename: L
authors.initials: L
authors.lastname: van den Heuvel
authors.forename: J
authors.initials: J
authors.lastname: Loeffen
authors.forename: R
authors.initials: R
authors.lastname: Smeets
authors.forename: F
authors.initials: F
authors.lastname: Trijbels
authors.forename: J
authors.initials: J
authors.lastname: Smeitink
mesh_terms: D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D042967:Electron Transport Complex I; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism; D018895:Microsatellite Repeats / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009245:NADH Dehydrogenase; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D011506:Proteins; D009247:NADH, NADPH Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone); D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C116384:NDUFA8 protein, human