Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of BRB-I-28 and its derivatives (GLG-V-13, SAZ-VII-22 and SAZ-VII-23), a novel group of antiarrhythmic agents, were investigated on the rat heart mitochondrial respiratory chain. The results indicate that BRB-I-28 and its derivatives have concentration-dependent inhibitory effects on NADH oxidase and NADH-CoQ reductase (complex I), but they have no significant effects on succinate oxidase, succinate dehydrogenase (complex II), CoQ-cytochrome c reductase (complex III), cytochrome c oxidase (complex IV), and NADH-K3Fe(CN)6 reductase. The site of inhibition of BRB-I-28 and its derivatives on the respiratory chain was localized between flavoprotein n (FPn) and CoQ, which is similar to the effect of rotenone and several other antiarrhythmic drugs such as amiodarone, propranolol, etc. BRB-I-28 and its derivatives also have significant inhibitory effects on mitochondrial ATPase activity as reported for other antiarrhythmic drugs such as amiodarone, propranolol, quinidine, and lidocaine. However, BRB-I-28 and its derivatives have no direct effects on sarcoplasmic reticulum Ca(2+)-ATPase activity. The inhibitory effects of BRB-I-28 and its derivatives on mitochondrial oxidative phosphorylation may result in the depletion of ATP. This effect, in combination with their effects on Na+,K(+)-ATPase, could possibly produce an increase in Ca2+ concentration in cytosol. This may be another mechanism by which these DHBCN derivatives produce an increase in systemic arterial blood pressure and contractile force of isolated cardiac muscle. On the other hand, inhibition on mitochondrial respiration may account for some of the potential toxic effects of these diheterabicyclo[3.3.1]nonane derivatives.
Res Commun Mol Pathol Pharmacol 1994 Aug
PMID:Effects of novel antiarrhythmic agents, BRB-I-28 and its derivatives, on the heart mitochondrial respiratory chain and sarcoplasmic reticulum Ca(2+)-ATPase. 799 64

Smoltification is the process whereby salmon alter their metabolism in preparation for movement from freshwater to seawater. Differential screening of a cDNA library prepared from post-smolt salmon liver mRNA led to the selection of a smoltification-induced sequence. Analysis of this cDNA revealed that it partially encoded subunit III of the enzyme cytochrome c oxidase. The complete coxIII sequence was amplified from salmon genomic DNA using consensus oligonucleotides based on ATPase 6 and tRNA(GLY) sequences from Pacific salmonid species. Cytochrome c oxidase subunit III liver mRNA levels were found to be significantly increased in salmon smolts. Northern blot analysis revealed a coxIII transcript of approximately 750 bp in all salmon tissues tested except blood. The DNA sequence of coxIII employs the mammalian mitochondrial genetic code and is strongly conserved when compared with that of other species.
Mol Mar Biol Biotechnol 1994 Aug
PMID:Cloning and sequencing of the Atlantic salmon (Salmo salar) cytochrome c oxidase subunit III gene (coxIII) and analysis of coxIII expression during parr-smolt transformation. 800 Apr 79

The nucleotide sequence of a cDNA corresponding to the transcription product of the mitochondrial structural gene cytochrome c oxidase subunit I was determined. A polypeptide of 508 residues was deduced from the reading frame established by the nucleotide sequence. TGA codes tryptophan, as in most other mitochondrial systems. From the comparison of the amino acid sequence of the putative Blattella germanica cytochrome c oxidase with those of Drosophila, we conclude that ATA and AGA codons specify methionine and serine respectively, instead of isoleucine and arginine. The sequence proposed for cytochrome c oxidase subunit I of B. germanica is largely homologous to that of other species. From the alignment of cytochrome c oxidase subunit I protein sequences we have found that 125 residues (positional identity of 22.3%) have remained invariant in this enzyme for more than one billion years of divergence. There is a developmental pattern of gene expression affecting the embryo stages. Northern blot analysis of RNA samples from different adult female tissues shows high cytochrome c oxidase subunit I mRNA levels in gut and fat body, and lower levels in ovary and colleterial glands.
Insect Biochem Mol Biol 1994 Jun
PMID:Cytochrome c oxidase subunit I from the cockroach Blattella germanica: cloning, developmental pattern and tissue expression. 804 76

The electron transport activities of various respiratory enzyme complexes in the muscle mitochondria of subjects of different ages without known mitochondriopathies were investigated. The results showed that the activity of cytochrome c oxidase declined with age more drastically than the activities of other respiratory enzyme complexes. NADH-cytochrome c reductase activity decreased mildly with age, whereas succinate cytochrome c reductase activity did not show significant age-dependent changes. Deletions in the muscle mitochondrial DNA (mtDNA) by use of PCR techniques were investigated. Three different age-dependent deletions in the muscle mtDNA of old individuals were found. These were identified to have sizes of 4,977 bp (8470 to 13446), 6,063 bp (7,842 to 13,904) and 7,436 bp (8,649 to 16,084). The 4,977 bp deleted mtDNA (dmtDNA) started to appear in the muscle mtDNA of subjects over 36 years of age and was found to exist in the muscle of more than 70% of the study subjects over 60 years of age. The 6,063 bp dmtDNA was detected in the muscle of the subjects above 25 years of age and was present in the muscle of about 91% of the individuals above 60 years old. However, the 7,436 bp deletion was less prevalent and was only seen in the muscle mtDNA of about 47.2% of the study subjects that were above 60 years. Using a quantitative PCR method, we found that the proportion of the 7,436 bp-deleted mtDNA increased with age, although with notable individual differences. Some of the subjects were found to have multiple deletions in their muscle mtDNAs, but some others carried only a specific type of deletion. The frequency of occurrence of multiple deletions in the muscle mtDNA was significantly increased with the age of the study subjects. The age-dependent increase in the proportions of various deleted mtDNA molecules may cause deleterious effects on the expression of mitochondrial genes in the muscle of old humans. This may account, at least in part, for the age-dependent decline of respiratory functions in the mitochondria of a broad spectrum of human tissues. We suggest that deletions of mtDNA are early molecular events that are associated with and contribute to the ageing processes of the human.
Biochem Mol Biol Int 1994 Apr
PMID:Age-dependent respiratory function decline and DNA deletions in human muscle mitochondria. 806 17

Cytochrome c oxidase was isolated from beef heart mitochondria by detergent extraction yielding two different crystal forms. Extraction with Triton detergents produced vesicular crystals with two-dimensional crystalline arrays of cytochrome c oxidase dimers while extraction with sodium deoxycholate produced crystalline sheets of cytochrome c oxidase monomers. The structures of both crystal forms were determined in two-dimensional projection along an axis normal to the plane of the membrane by cryoelectron microscopy of crystals embedded in vitreous ice (frozen-hydrated). The projection structures of unstained frozen hydrated monomers and of dimers are similar to the structures of the crystals in negative stain. The molecular outline of dimers can be approximated by a parallelogram 44 A by 82 A with an included angle of 80 degrees. Monomers are less regular consisting of two large domains with a smaller domain at one end and a total length of approximately 82 A. Comparison of the two structures reveals the orientation of cytochrome c oxidase monomers within dimers, an orientation which is different from earlier models of monomer-monomer interaction, and suggests a very close interaction between monomers when they associate to form dimers. The crystalline sheets of cytochrome c oxidase monomers bind tightly the small peripheral membrane protein substrate, cytochrome c, and this binding accentuates a tendency of these crystals to stack upon one another. Images of crystals of the cytochrome c oxidase/cytochrome c complex were analyzed by crosscorrelation analysis versus the monomer crystal image. Two types of two-layer crystals have been identified. Both types have one layer rotated by 180 degrees with respect to the other, but they differ in the shifts of origin along crystal axes of the two layers. Difference images formed by subtracting simulated multilayered crystal images (which have no bound cytochrome c) from the complex crystals (cytochrome c oxidase plus cytochrome c) contain one positive difference peak for each cytochrome oxidase monomer within a unit cell. Comparison of the difference peak loci among the different crystal forms is interpreted based upon a consensus cytochrome c binding site in the single layer cytochrome oxidase monomer crystal image.
J Mol Biol 1994 Apr 01
PMID:Electron microscopy of cytochrome c oxidase crystals. Monomer-dimer relationship and cytochrome c binding site. 814 42

A metabolic investigation was carried out in an eight-month old infant with intrauterine hypotrophia, failure to thrive, psychomotoric retardation and cerebral atrophy, who died after respiratory infections. Blood analysis revealed intermittent lactic acidosis with normal lactate/pyruvate ratio. Activities of cytochrome c oxidase in skeletal muscle, heart, liver and fibroblasts were all in the reference range of controls. Activity of pyruvate dehydrogenase complex (PDH) was decreased in muscle homogenate, heart and liver mitochondria but was normal in cultured skin fibroblasts. Immunodetection of PDH subunits, and assay of El alpha phosphorylation showed in the patient decrease of E1 alpha in skeletal muscle, and enhanced level of E1 alpha phosphorylation in liver mitochondria.
Biochem Mol Biol Int 1993 Dec
PMID:Deficiency of pyruvate dehydrogenase complex in tissues of an eight month old infant. 819

We report here the discovery of a novel bacterial gene (cycH) whose product is involved in the biogenesis of most of the cellular cytochromes c. The cycH gene was detected in the course of characterizing a cytochrome oxidase-deficient Bradyrhizobium japonicum Tn5 mutant (strain COX3) in which the transposon insertion disrupted cycH. All of the c-type cytochromes detectable in aerobically grown B. japonicum wild-type cells were absent in the COX3 mutant, with the exception of cytochrome c1. A secondary phenotypic effect was the spectroscopic absence of the aa3-type cytochrome c oxidase. The nucleotide sequence of the cloned wild-type cycH gene predicted a membrane-bound 369-amino-acid protein with an M(r) of 39727. Results from studies on its membrane topology suggested that approximately 110 N-terminal amino acids are involved in anchoring the protein in the membrane, whereas the remaining two-thirds of the protein are exposed to the periplasm. We postulate that the CycH protein plays an essential role in an as yet unidentified periplasmic step in the biogenesis of holocytochromes c, except that of cytochrome c1.
Mol Microbiol 1993 Aug
PMID:Formation of several bacterial c-type cytochromes requires a novel membrane-anchored protein that faces the periplasm. 823 5

The germinating asexual spores (conidia) of Neurospora crassa were employed to study steps in the accumulation of transcripts of groups of mitochondrial genes, including those for peptide subunits of cytochrome c oxidase (CO), ATPase (ATP), and apocytochrome b (COB). Physically clustered groups of genes were expressed as cohorts: transcripts of the ATP8-ATP6-mtATP9-CO2 genes were almost undetectable in the dormant spores, and they accumulated rapidly as a group immediately after spore activation. Transcripts of COB and the adjacent CO1 were abundant in the dormant spores, and the dormant and germinating spores contained size forms of the COB transcripts that were not evident in vegetative cells. Polyribosomes were prepared from mitochondrial lysates, and the polyribosomal RNA was probed to identify the mRNAs of specific genes; in several instances polycistronic mRNAs were present in the polyribosomes as were the smaller end-products of the inferred transcript processing pathways. The expression of the physically dispersed genes for subunit peptides of cytochrome c oxidase appears to be regulated to the level of translation; these transcripts are accumulated in the total mitochondrial RNA with sharply different kinetics, but they appeared in the polyribosomes uniformly, their appearance correlating with the uniform synthesis of the subunit peptides. Transcripts for a previously reported non-functional mitochondrial gene, homologous to the functional nuclear gene for ATPase subunit 9, were found in the germinating spores, but were not detected in vegetative cells. These mtATP9 transcripts were also present in the polyribosomes and were apparently translated into a protein in vivo whose synthesis was insensitive to cycloheximide and detectable with an anti-ATP9 subunit antibody. Transcripts for two nuclear genes for mitochondrially localized proteins, ATP9 and CO5, were accumulated in unison and especially rapidly during spore germination.
J Mol Biol 1994 Jan 21
PMID:Expression of mitochondrial genes in the germinating conidia of Neurospora crassa. 828 26

Strong heterologous hybridization of a synthetic oligonucleotide probe of 17 bp originally used to clone subunit I of the Paracoccus denitrificans cytochrome c oxidase (M. Raitio, T. Jalli and M. Saraste (1987) EMBO J. 6, 2825-2833) to a single band was observed on Southern blots of Anacystis nidulans R2 (Synechococcus PCC 7942), Synechocystis PCC 6803, and Nostoc Mac PCC 8002 chromosomal DNA digests. Six pooled gene banks prepared from Synechocystis PCC 6803 contained regions that hybridized to the oligonucleotide (probe C) which is specifically directed toward the putative Cu-binding site VWAHHMY of subunit I. Two of these gene banks were transformed into Escherichia coli and screened for colonies hybridizing to probe C. Several clones were recovered, and one type of plasmid was identified from each gene bank. The two (overlapping) plasmids were called pDAUV1 and pDAUV2. A restriction map of the plasmids showed that the overlapping region contained an 80 bp PvuI-KpnI fragment binding to probe C. The two clones together permitted sequencing of the entire gene for cytochrome c oxidase subunit I from Synechocystis PCC 6803. Further systematic sequencing of approximately 1000 bp upstream and downstream each of the ctaD (subunit I) gene revealed the presence of two genes encoding subunits II (ctaC gene) and III (ctaE gene) due to conspicuous similarities to homologous genes from other cytochrome c oxidase-containing organisms. Yet, no indications of genes encoding additional subunits of the oxidase were found within the region sequenced.
Biochem Mol Biol Int 1993 Mar
PMID:Characterization of a cta/CDE operon-like genomic region encoding subunits I-III of the cytochrome c oxidase of the cyanobacterium Synechocystis PCC 6803. 838 68

Translation of the Saccharomyces cerevisiae mitochondrial COX3 mRNA, encoding subunit III of cytochrome c oxidase, specifically requires the action of the nuclear gene products PET54, PET122, and PET494 at a site encoded in the 612-base 5' untranslated leader. To identify more precisely the site of action of the translational activators, we constructed two large deletions of the COX3 mRNA 5' untranslated leader. Both deletions blocked translation without affecting mRNA stability. However, one of the large deletions was able to revert to partial function by a small secondary deletion within the remaining 5' leader sequences. Translation of the resulting mutant (cox3-15) mRNA was still dependent on the nuclear-encoded specific activators but was cold sensitive. We selected revertants of this mitochondrial mutant at low temperature to identify genes encoding proteins that might interact with the COX3 mRNA 5' leader. One such revertant carried a missense mutation in the PET122 gene that was a strong and dominant suppressor of the cold-sensitive defect in the mRNA, indicating that the PET122 protein interacts functionally (possibly directly) with the COX3 mRNA 5' leader. The cox3-15 mutation was not suppressed by overproduction of the wild-type PET122 protein but was very weakly suppressed by overproduction of PET494 and slightly better suppressed by co-overproduction of PET494 and PET122.
Mol Cell Biol 1993 Aug
PMID:Suppression of a defect in the 5' untranslated leader of mitochondrial COX3 mRNA by a mutation affecting an mRNA-specific translational activator protein. 839 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>