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.

Proteomic analysis unveils a FANCA-modulated neddylation pathway involved in CXCR5 membrane targeting and cell mobility

“…1E; supplementary material Table S3). These three proteins were FANCD2, FANCI and the nuclear-encoded NDUFA8 subunit of NADH:ubiquinone oxidoreductase, which is part of the first mitochondrial respiratory chain complex (Triepels et al, 1998). Only FANCD2 and FANCI, however, had a highly significant FANC-corrected:FANC-deficient ratio, which was consistent with their already known direct ubiquitylation by the FANCcore complex.…”

Analysis of the liver mitochondrial proteome in response to ethanol andS-adenosylmethionine treatments: novel molecular targets of disease and hepatoprotection

“…For example, complex I, subcomplex 12 (a.k.a. B17.2) is thought to play a key chaperone-like role in complex I assembly (31,60). Therefore, the ethanol-mediated decrease in these nuclear encoded subcomplexes may explain, in part, the overall decrease in total complex I protein in response to chronic ethanol exposure.…”

Unique Metabolic Features of Stem Cells, Cardiomyocytes, and Their Progenitors

“…98 NADH dehydrogenase (Ubiquinone) 1, α/β subcomplex, 1, 8 kDa (NDUFAB1) is also a mitochondrial protein subcomplex that is involved in the transfer of electrons from NADH to the respiratory chain. 99 Protein kinase, AMP-activated, α-2 catalytic subunit (PRKAA2) activates many catabolic pathways, including fatty acid metabolism, to ensure a high levels of ATP production. 100 Enoyl-CoA Δ-isomerase 1 (Dci) encodes for a key mitochondrial protein involved in the β-oxidation of unsaturated fatty acids.…”

“…Protein phosphatase 1, regulatory subunit 3C (PPP1R3C), phosphorylase, glycogen, muscle (PYGM), enolase 3 (β, muscle; ENO3), phosphoglycerate mutase 2 (muscle; PGAM2), and amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL) regulate the degradation of glycogen into glucose (glycogenolysis). 99,[101][102][103][104][105][106][107][108] Phosphofructokinase, muscle (PFKM) catalyzes the phosphorylation of fructose-6-phosphate during glycolysis. 104 Malate dehydrogenase 1 (MDH1) is involved in gluconeogenesis.…”