Tissue-specific expression and chromosome assignment of genes specifying two isoforms of subunit VIIa of human cytochrome c oxidase

Arnaudo, Enrica; Hirano, Michio; Sedan, R. Sathiagana; Milatovich, Athena; Hsieh, Chih Lin; Fabrizi, Gian Maria; Grossman, Lawrence I.; Francke, Uta; Schon, Eric A.

doi:10.1016/0378-1119(92)90287-y

Cited by 65 publications

(23 citation statements)

References 32 publications

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“…To analyse the transcription of the three mitochondrial subunits (I, I1 and 111) [43] as well as nuclear subunits VIb [44], VIc [45], VIII [21] and VIIaH [27] probes were prepared according to the published nucleotide sequences by the polymerase chain reaction (PCR) [46]. Mitochondria1 DNA of human placenta was used as template for amplification of DNA for mitochondrial subunits (I, 11, and 111) and a human skeletal muscle cDNA library for amplification of DNA coding for nuclear subunits (VIb, VIc, VIIaH and VIII).…”

Section: Probesmentioning

confidence: 99%

Expression of human cytochrome c, oxidase subunits during fetal development

Bonne

Seibel²,

Possekel

et al. 1993

European Journal of Biochemistry

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Expression of human cytochrome c oxidase (COX) subunits was examined at fetal (20-28 weeks) and adult state by Northern blot hybridization with mRNA from liver, heart, skeletal muscle, and intestine. The data were related to COX and citrate synthase activities and to immunodetected COX subunits (II/III, IV, VIIaH). In liver little changes of COX transcripts are observed from fetal to adult state. In contrast, in heart and skeletal muscle all transcripts of COX subunits increase between 2-20-fold, when related to the amount of 28s rRNA. In fetal heart and skeletal muscle the relative amounts of the liver-type transcripts of subunit VIa were 30% and 25% from total VIa transcripts (VIaL + VIaH), respectively, but decrease to only 2-5% at adult state. The liver-type transcripts of subunit VIIa occur to 50% in fetal heart and skeletal muscle, which remained unchanged in adult heart and decrease to 5 8 % in adult skeletal muscle. The results clearly indicate a switch of gene expression in heart and skeletal muscle during development, from the liver type to the headmuscle type of subunit VIa (and partly VIIa).Cytochrome c oxidase (COX) is the terminal enzyme complex of the respiratory chain, coupling the transfer of electrons from cytochrome c to molecular oxygen with the concomitant production of a proton electrochemical gradient across the inner mitochondrial membrane [l]. In mammals, the enzyme consists of 13 dissimilar polypeptides [ 2 ] . The three largest subunits (1-111) are encoded by the mitochondrial genome and constitute the catalytic core of the enzyme [3, 41. The ten smaller nuclear gene products [S] have been suggested to play a keyrole in the regulation of the enzyme [6, 71. Recently it was demonstrated [8, 91 that the activity and energy transduction of COX from heart and skeletal muscle is tissue-specific and regulated by nucleotides via interaction with subunit VIaH (heart/muscle type).The mammalian COX occurs in tissue-specific isoforms differing in the isotype of subunits VIa, VIIa and/or VIII (liver type or heart/muscle type). This has been demonstrated by immunological, electrophoretic and amino acid sequence differences between corresponding nuclear-coded subunits of COX from different mammalian tissues and species [2, 5, 101. These findings have been confirmed by cloning and sequencing of cDNAs coding for the different subunits of tissue-specific isoforms for subunit VIa of rat [ I l l , VIIa [lo,12, 161 and VIII [lo, 131 occur as liver (L) and heart (H) isoforms. In rat only the L form of subunit VIIa was found [17, 181, but both isoforms of subunits VIa [ l l ] and VIII [19]. In human, subunit VIII is present only in the L form [20, 211, whereas both isoforms occur for subunits VIa [22, Most of the other nuclearcoded subunits have been cloned and sequenced from rat, beef and human (for review see [28, 291).A co-ordinate expression of the mitochondrial-coded subunit 111 and the nuclear-coded subunit VIc has been demonstrated in rat tissues under steady-state conditions [30-321. Under non-s...

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Section: Probesmentioning

confidence: 99%

Expression of human cytochrome c, oxidase subunits during fetal development

Bonne

Seibel²,

Possekel

et al. 1993

European Journal of Biochemistry

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“…COX7A1 is located on chromosome 19q13.12 within a CpG dense region [6] where tissue-specific DNA methylation has been correlated with gene expression [7]. COX7A1 is only expressed in skeletal and heart muscle [8], and is significantly downregulated in diabetic muscle [3].…”

Section: Introductionmentioning

confidence: 99%

Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle

et al. 2008

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Aims/hypothesis Reduced oxidative capacity of the mitochondria in skeletal muscle has been suggested to contribute to insulin resistance and type 2 diabetes. Moreover, a set of genes influencing oxidative phosphorylation (OXPHOS) is downregulated in diabetic muscle. Here we studied whether genetic, epigenetic and non-genetic factors influence a component of the respiratory chain, COX7A1, previously shown to be downregulated in skeletal muscle from patients with type 2 diabetes. The specific aims were to: (1) evaluate the impact of genetic (single nucleotide polymorphisms [SNPs]), epigenetic (DNA methylation) and non-genetic (age) factors on the expression of COX7A1 in human skeletal muscle; and (2) investigate whether common variants in the COX7A1 gene are associated with increased risk of type 2 diabetes. Methods COX7A1 mRNA expression was analysed in muscle biopsies from young (n=110) and elderly (n=86) non-diabetic twins and related to measures of in vivo metabolism. Genetic variants (three SNPs) from the COX7A1 locus were genotyped in the twins and in two independent type 2 diabetes case-control cohorts (n=1466 and 6380, respectively). DNA methylation of the COX7A1 promoter was analysed in a subset of twins (ten young, ten elderly) using bisulphite sequencing. Results While DNA methylation of the COX7A1 promoter was increased in muscle from elderly compared with young twins (19.9±8.3% vs 1.8±2.7%; p=0.035), the opposite was found for COX7A1 mRNA expression (elderly 1.00±0.05 vs young 1.68 ± 0.06; p = 0.0005). The heritability of COX7A1 expression was estimated to be 50% in young and 72% in elderly twins. One of the polymorphisms investigated, rs753420, influenced basal COX7A1 expression in muscle of young (p=0.0001) but not of elderly twins. The transcript level of COX7A1 was associated with increased in vivo glucose uptake and V : O 2max (p=0.009 and p=0.001, respectively). We did not observe any genetic association between COX7A1 polymorphisms and type 2 diabetes after correcting for multiple testing. Diabetologia (2008) Conclusions/interpretation Our results provide further evidence for age as a factor influencing DNA methylation and expression of OXPHOS genes, and thereby in vivo metabolism.

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“…It is tempting to speculate that the divergence in the amino-terminal domains of SIG81 and COX7a reflect distinct intramitochondrial localization and thus justify the occurrence of two highly homologous proteins being coincidentally expressed in the same tissue. It is peculiar that, if SIG81 arose from the duplication of an ancestral gene, it has maintained a widespread expression in various tissues instead of exhibiting the more specialized pattern such as that for COX7a-H (10,36) and by many other genes that arise by duplication. The tight regulation of SIG81 gene expression is exemplified by the fact that no measurable differences were found in mRNA levels in RAW 264.7 and J774A.1 macrophages and NIH 3T3 fibroblasts that were serum-starved and then growth-stimulated by addition of serum to increase their metabolic rates.…”

Section: Discussionmentioning

confidence: 99%

“…SIG81 proteins also contain the motif ELQKFFQKAD (amino acids 61-70) homologous to the sequence EKQKLFQED proposed as a functional core domain in mammalian COX7a (10). However, in nonmammalian vertebrates such as rainbow trout, COX7a-L contains the slightly modified sequence EKQKLFQAX (37) whereas in yeast COX7a, homologies in this region are reduced just to the amino acid pairs QK and FQ (10,36), thus suggesting that a great deal of (1 l, 300 g/ml) from glutathione-Sepharose gel obtained from pGEX3X-transformed bacteria after a 6-h induction with IPTG; lanes 2, postnuclear supernatant (100 g of total protein) from mouse liver obtained after a 750 ϫ g centrifugation as described under "Experimental Procedures." Proteins were electrophoresed in a high resolution SDS-PAGE gel (29) and electrophoretically transferred to Hybond polyvinylidene difluoride membrane without staining, and then detected with rabbit preimmune serum (A) or affinity-purified anti-GST-SIG81 antibodies (B).…”

Section: Discussionmentioning

confidence: 99%

Identification of an Additional Member of the Cytochrome c Oxidase Subunit VIIa Family of Proteins

Segade

Hurlé²,

Claudio³

et al. 1996

Journal of Biological Chemistry

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We report the cloning, nucleotide sequence, evolutionary analysis, and intracellular localization of SIG81, a silica-induced cDNA from mouse macrophages. The cDNA encodes a 111-amino acid protein with extensive sequence identity with members of the mammalian cytochrome c oxidase subunit VIIa (COX7a) family. A human SIG81 sequence >80% identical with the mouse cDNA was deduced from homologous sequences in the human expressed tags data base. The deduced aminoterminal region shows features common to mitochondrial targeting sequences. A phylogenetic analysis of the carboxyl-terminal domain homologous to COX7a identifies SIG81 as a divergent member of the family with an ancient origin. Southern blot analysis showed that the mouse genome contains two to three copies of the SIG81 gene. Northern blot analysis revealed that the SIG81 transcript is approximately 1 kb and expressed in every tissue tested, with higher levels of expression observed in kidney and liver. Antibodies raised against a glutathione S-transferase SIG81 fusion protein detected a 13.5-kDa protein that co-fractionates with mitochondrial localized enzymatic activity. Taken together, our data suggest that SIG81 is a novel member of the COX7a family that is constitutively expressed in mouse cells.

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Tissue-specific expression and chromosome assignment of genes specifying two isoforms of subunit VIIa of human cytochrome c oxidase

Cited by 65 publications

References 32 publications

Expression of human cytochrome c, oxidase subunits during fetal development

Expression of human cytochrome c, oxidase subunits during fetal development

Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle

Identification of an Additional Member of the Cytochrome c Oxidase Subunit VIIa Family of Proteins

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