Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to investigate the contribution of mitochondrial and cytoplasmic protein synthesis to the biogenesis of cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase EC 1.9.3.1) and rutamycin-sensitive adenosine triphosphatase (ATP phosphohydrolase EC 3.6.1.3) in cultured oocytes of the toad, Xenopus laevis. X. laevis cytochrome oxidase was purified over 23-fold with respect to specific activity and over 29-fold with respect to specific heme a content from oocyte submitochondrial particles. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate separated the enzyme into six subunits with molecular weights of 44,000, 33,000, 23,000, 17,000, 12,000 and 9,500. the synthesis of the three larger subunits is sensitive to chloramphenicol (an inhibitor of mitochondrial protein synthesis), indicating that these subunits are made on mitochondrial ribosomes; the synthesis of the three smaller subunits is sensitive to cycloheximide (an inhibitor of cytoplasmic protein synthesis) and therefore occurs on cytoplasmic ribosomes. X. laevis rutamycin-sensitive ATPase, purified over 19-fold from oocyte submitochondrial pparticles, consists of 10 subunits with molecular weights of 56,000, 53,000, 41,000, 32,000, 29,000, 24,000, 21,000, 17,500 (2), and 11,500 on sodium dodecyl sulfate-polyacrylamide gels. The 29,000, 21,000, and one of the 17,500-dalton polypeptides are synthesized in the presence of cycloheximide and are, therefore, products of mitochondrial protein synthesis; the synthesis of the remaining seven subunits occurs in the presence of chloramphenicol, indicating that these subunits are made on cytoplasmic ribosomes. The synthesis of protein by mitochondria in cultured oocytes appears to be dependent upon cytoplasmic protein synthesis. In the presence of cycloheximide, the mitoribosomal synthesis of the subunits of cytochrome oxidase and rutamycin-sensitive ATPase is detectable only after a prior inhibition of mitochondrial protein synthesis by chloramphenicol. Oocyte mitochondrial ribosomes synthesize at least nine polypeptides after chloramphenicol treatment, three of which are components of neither cytochrome oxidase nor rutamycin-sensitive ATPase.
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PMID:Synthesis of the mitochondrial inner membrane in cultured Xenopus laevis oocytes. 18 93

The DNA sequence and derived amino-acid sequence of a 5618-base region in the 74-min area of the Escherichia coli chromosome has been determined in order to locate the structural gene, nirB, for the NADH-dependent nitrite reductase and a gene, cysG, required for the synthesis of the sirohaem prosthetic group. Three additional open reading frames, nirD, nirE and nirC, were found between nirB and cysG. Potential binding sites on the NirB protein for NADH and FAD, as well as conserved central core and interface domains, were deduced by comparing the derived amino-acid sequence with those of database proteins. A directly repeated sequence, which includes the motif -Cys-Xaa-Xaa-Cys-, is suggested as the binding site for either one [4Fe-4S] or two [2Fe-2S] clusters. The nirD gene potentially encodes a soluble, cytoplasmic protein of unknown function. No significant similarities were found between the derived amino-acid sequence of NirD and either NirB or any other protein in the database. If the nirE open reading frame is translated, it would encode a 33-amino-acid peptide of unknown function which includes 8 phenylalanyl residues. The product of the nirC gene is a highly hydrophobic protein with regions of amino-acid sequence similar to cytochrome oxidase polypeptide 1.
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PMID:Nucleotide sequence, organisation and structural analysis of the products of genes in the nirB-cysG region of the Escherichia coli K-12 chromosome. 220 Jun 72

The third-chromosome mutation Killer of prune (K-pn) causes no phenotype by itself, but causes lethality in individuals homozygous for the nonlethal X-chromosome mutation prune (pn). We have recovered 12 gamma-ray-induced revertants of Killer of prune. All of the revertants fail to complement a recessive cell lethal mutation in the abnormal wing discs (awd) gene. We present evidence that Killer of prune is a mutation in the awd gene. First, revertant awdKR14 leads to reduced accumulation of the awd gene product, but does not affect flanking genes. Second, when a copy of the awd gene is cloned from Killer of prune homozygous flies and injected into embryos, transformants express the lethal interaction with prune. In individuals of the genotype pn; awdK-pn/awd+ the awd mRNA is present at normal levels but the awd polypeptide fails to accumulate. The absence of the awd gene product in such individuals is the cause of death. Although the awd polypeptide is a subunit of a cytoplasmic protein, its sequence is similar to subunit V of yeast cytochrome oxidase.
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PMID:Analysis of the lethal interaction between the prune and Killer of prune mutations of Drosophila. 284 80

The mechanism of cytochrome induction in human cells was investigated. Cultured fibroblasts grown in low oxygen had markedly reduced contents of cytochromes A + A(3), B, and C + C(1) as measured by absorption spectra. Chloramphenicol but not cycloheximide or actinomycin blocked the initial increase in cytochrome oxidase activity in cells shifted from low to ambient oxygen, suggesting that initiation of enzyme induction requires mitochondrial but not cytoplasmic protein synthesis or transcription of nuclear genes. Turnover of cytochrome oxidase was demonstrated in cells in stationary phase.
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PMID:Induction of cytochromes in human cells by oxygen. 431 97

Cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1), the terminal oxidase of the respiratory chain in eucaryotic cells, has been purified from human placenta mitochondria. Seven polypeptides have been identified reproducibly by high-resolution electrophoresis of the enzyme complex through sodium dodecyl sulfate (Na-DodSO4)--urea polyacrylamide gels; these correspond closely in size to the subunits of beef heart cytochrome c oxidase. When HeLa cells, grown in suspension culture, were pulse-labeled with [35S]methionine in the presence of cycloheximide to inhibit cytoplasmic protein synthesis and chased with an excess of unlabeled methionine in the absence of the drug, the mitochondrially synthesized polypeptides were resolved into at least 17 components by NaDodSO4--urea polyacrylamide gel electrophoresis. After labeled HeLa mitochondria were mixed with human placenta mitochondria and the cytochrome c oxidase was isolated, three of the labeled components were found to copurify with the three largest subunits of the complex. We conclude that human cytochrome c oxidase contains seven subunits, the three largest of which are synthesized on mitochondrial ribosomes, while the other four are synthesized in the cytoplasm.
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PMID:Isolation, subunit composition, and site of synthesis of human cytochrome c oxidase. 624 17

Mutations in the COX17 gene of Saccharomyces cerevisiae cause a respiratory deficiency due to a block in the production of a functional cytochrome oxidase complex. Because cox17 mutants are able to express both the mitochondrially and nuclearly encoded subunits of cytochrome oxidase, the Cox17p most likely affects some late posttranslational step of the assembly pathway. A fragment of yeast nuclear DNA capable of complementing the mutation has been cloned by transformation of the cox17 mutant with a library of genomic DNA. Subcloning and sequencing of the COX17 gene revealed that it codes for a cysteine-rich protein with a molecular weight of 8,057. Unlike other previously described accessory factors involved in cytochrome oxidase assembly, all of which are components of mitochondria, Cox17p is a cytoplasmic protein. The cytoplasmic location of Cox17p suggested that it might have a function in delivery of a prosthetic group to the holoenzyme. A requirement of Cox17p in providing the copper prosthetic group of cytochrome oxidase is supported by the finding that a cox17 null mutant is rescued by the addition of copper to the growth medium. Evidence is presented indicating that Cox17p is not involved in general copper metabolism in yeast but rather has a more specific function in the delivery of copper to mitochondria.
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PMID:Characterization of COX17, a yeast gene involved in copper metabolism and assembly of cytochrome oxidase. 866 33

C129/U1 is a respiratory defective mutant of Saccharomyces cerevisiae arrested in cytochrome oxidase assembly due to a mutation in COX17, a nuclear gene encoding a low molecular weight cytoplasmic protein proposed to function in mitochondrial copper recruitment. In the present study we show that the respiratory defect of C129/U1 is rescuable by two multicopy suppressors, SCO1 and SCO2. SCO1 was earlier reported to code for a mitochondrial inner membrane protein with an essential function in cytochrome oxidase assembly (Buchwald, P., Krummeck, G., and Rodel, G. (1991) Mol. Gen. Genet. 229, 413-420). SCO2 is a homologue of SCO1, whose product is also localized in the mitochondrial membrane but is not required for respiration. SCO1 also suppresses a cox17 null mutant, indicating that overexpression of Sco1p can compensate for the absence of Cox17p. In contrast, neither copper, COX17 on a multicopy plasmid, or a combination of the two is able to restore respiration in sco1 mutants. Rescue of cox17 mutants by Sco1p suggests that this mitochondrial protein plays a role either in mitochondrial copper transport or insertion of copper into the active site of cytochrome oxidase. Although SCO2 can also partially restore respiratory growth in the cox17 null mutant, rescue in this case requires addition of copper to the growth medium. SCO2 does not suppress a sco1 null mutant, although it is able to partially rescue a sco1 point mutant. We interpret the ability of SCO2 to restore respiration in cox17, but not in sco1 mutants, to indicate that Sco1p and Sco2p have overlapping but not identical functions.
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PMID:SCO1 and SCO2 act as high copy suppressors of a mitochondrial copper recruitment defect in Saccharomyces cerevisiae. 870 95

We have identified an RNA species that appears to be induced by oxidative stress in hamster HA-1 fibroblasts using the differential display technique, but instead is found to be degraded when evaluated by Northern blot hybridization. Cloning and subsequent sequencing identified the partially degraded RNA as 16S ribosomal RNA (rRNA), a major component of mitochondrial ribosomes. Degradation, and associated decreases in the levels of the mature- and precursor-species of 16S rRNA, appear to be dependent upon calcium, but not cytoplasmic protein synthesis nor nuclear transcription. Other decreased mitochondrial RNAs were also identified, including 12S rRNA, NADH dehydrogenase subunit 6, ATPase subunit 6, and cytochrome oxidase subunits I and III. A significant part of many, if not all, of these RNA decreases was due to degradation. As compared with 16S rRNA, significantly less degradation was observed for cytoplasmic 28S/18S rRNAs, even at very high peroxide concentration. Analysis of 21 cytoplasmic mRNAs revealed little or no decrease in mature band signal in response to peroxide, and several cytoplasmic mRNAs were actually up-regulated. Thus, a preferential down-regulation of mitochondrial RNAs occurs in HA-1 fibroblasts in response to hydrogen peroxide. Subcellular fractionation analysis, using 16S rRNA degradation as a gauge, indicates that this down-regulation is specific to mitochondria. The down-regulation of mitochondrial RNAs may represent a general mechanism by which cells protect themselves against oxidative stress.
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PMID:Down-regulation of mammalian mitochondrial RNAs during oxidative stress. 898 Oct 48

The COX17 gene of Saccharomyces cerevisiae codes for a cytoplasmic protein essential for the expression of functional cytochrome oxidase. This protein has been implicated in targeting copper to mitochondria. To determine if Cox17p is present in mammalian cells, a yeast strain carrying a null mutation in COX17 was transformed with a human cDNA expression library. All the respiratory competent clones obtained from the transformations carried a common cDNA sequence with a reading frame predicting a product homologous to yeast Cox17p. The cloning of a mammalian COX17 homolog suggests that the encoded product is likely to function in copper recruitment in eucaryotic cells in general. Its presence in humans provides a possible target for genetically inherited deficiencies in cytochrome oxidase.
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PMID:Isolation of a cDNA encoding the human homolog of COX17, a yeast gene essential for mitochondrial copper recruitment. 905 Sep 18

One of the central tenets in neuroscience has been that the protein constituents of distal compartments of the neuron (e.g., the axon and nerve terminal) are synthesized in the nerve cell body and are subsequently transported to their ultimate sites of function. In contrast to this postulate, we have established previously that a heterogeneous population of mRNAs and biologically active polyribosomes exist in the giant axon and presynaptic nerve terminals of the photoreceptor neurons in squid. We report that these mRNA populations contain mRNAs for nuclear-encoded mitochondrial proteins to include: cytochrome oxidase subunit 17, propionyl-CoA carboxylase (EC 6.4.1.3), dihydrolipoamide dehydrogenase (EC 1.8.1.4), and coenzyme Q subunit 7. The mRNA for heat shock protein 70, a chaperone protein known to be involved in the import of proteins into mitochondria, has also been identified. Electrophoretic gel analysis of newly synthesized proteins in the synaptosomal fraction isolated from the squid optic lobe revealed that the large presynaptic terminals of the photoreceptor neuron contain a cytoplasmic protein synthetic system. Importantly, a significant amount of the cycloheximide resistant proteins locally synthesized in the terminal becomes associated with mitochondria. PCR analysis of RNA from synaptosomal polysomes establishes that COX17 and CoQ7 mRNAs are being actively translated. Taken together, these findings indicate that proteins required for the maintenance of mitochondrial function are synthesized locally in the presynaptic nerve terminal, and call attention to the intimacy of the relationship between the terminal and its energy generating system. J. Neurosci. Res. 64:447-453, 2001. Published 2001 Wiley-Liss, Inc.
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PMID:Local synthesis of nuclear-encoded mitochondrial proteins in the presynaptic nerve terminal. 1139 99


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