Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.3 (complex I)
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Analyses of the Trypanosoma equiperdum (ATCC 30019) maxicircle reveals deletions, duplications and rearrangement compared to T. brucei. The genes for 9S rRNA and 12 proteins are absent. The 12S rRNA and cytochrome oxidase subunit I (COI) genes lack their 3' ends and are adjacent indicating deletion of intervening genes. The remaining two NADH dehydrogenase subunit genes (ND4 and ND5), the ribosomal protein RPS12 gene and the CR5 gene are duplicated and rearranged. ND4, RPS12 and the CR4 transcripts are abundant in steady state RNA while 12S rRNA and COI transcripts are not detected. Full length ND5 transcripts are rare, if present, but chimeric ND5/ND4 transcripts are abundant. The CR4 and RPS12 transcripts are the size of unedited RNAs suggesting that they are processed. However, they are not edited normally, presumably due to the absence of minicircle gRNA genes.
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PMID:Mitochondrial transcripts are processed but are not edited normally in Trypanosoma equiperdum (ATCC 30019) which has kDNA sequence deletion and duplication. 820 73

We previously reported the sequencing of two genes (ndhA and ndhI) encoding two of the subunits of the type-I NADH-ubiquinone oxidoreductase from Rhodobacter capsulatus (Rc). The present paper deals with the cloning and characterization of a chromosomal fragment clustering five new Rc genes which encode subunits of this enzyme. This gene cluster is located immediately downstream from ndhA and ndhI, and also contains two unidentified open reading frames (urf2, urf3). The five genes, nuoJ, nuoK, nuoL, nuoM and nuoN, encode proteins related, respectively, to mitochondrial (mt) subunits ND6, ND4L, ND5, ND4 and ND2. The overall organization of the nuo genes identified in Rc shows similarity to that of the Paracoccus denitrificans (Pd) nqo gene cluster.
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PMID:Identification of five Rhodobacter capsulatus genes encoding the equivalent of ND subunits of the mitochondrial NADH-ubiquinone oxidoreductase. 856 20

For long time, it has been believed that the yeast mitochondrial (mt) genome lacks NADH dehydrogenase subunit genes which are designated ND genes. However, our complete mtDNA sequencing of yeast Hansenula wingei led us to the first finding of seven mitochondrial ND genes. We investigated the distribution of ND genes in mtDNAs of other yeasts including Pichia membranaefaciens, Yarrowia lypolitica, Candida maltosa, Saccharomyces kluyveri and Saccharomyces exiguus. By Southern hybridization with probes of H. wingei's ND1, 2 and 5 genes, we detected positive signals on mtDNAs in P. membranaefaciens, Y. lypolitica, and C. maltosa. To confirm this, we cloned and sequenced DNA fragment of ND5 gene in P. membranaefaciens. We have discussed the sequence homology and genome structure.
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PMID:The distribution of ND genes in yeast mitochondrial genomes and the mitochondrial DNA structure of Pichia membranaefacens. 884 33

Inefficiencies in mitochondrial respiration mainly affecting complex I and IV activities, occur with increasing age and have been suggested as a possible etiological factor in age-related neurodegenerative diseases. It has been suggested that this finding may be explained by an accumulation of mtDNA mutations. We hypothesise that some polymorphic mitochondrial genomes encode less efficient respiratory protein subunits and are therefore less tolerant of acquired mutations. If this hypothesis is correct, individuals with 'less efficient' mtDNA genotypes may be predisposed both to more rapid biological aging and to neurodegenerative disease. In this study we investigate the substantia nigra mtDNA composition from 4 elderly individuals (2 non-parkinsonian and 2 with idiopathic Parkinson's disease) to determine whether there is sufficient polymorphism to account for different possible respiratory efficiencies. THe mitochondrial tRNAArg, tRNAHis, tRNAScr, tRNALeu(CUN), ND4L, ND4 and ND5 genes as well as parts of the ND3 and ND6 subunit coding regions were analysed (4221 bp), revealing the presence of multiple deletions and 48 discrete polymorphic sites. These included 23 missense, two tRNA and one nonsense polymorphism. Eight of the missense polymorphisms caused nonconservative amino acid replacements at sites of moderate to high evolutionary constraint. These findings suggest that mtDNA diversity in the ageing brain may account for a range of bioenergetic outcomes. The variation in mtDNA genotype involves both inherited (fixed familial) polymorphism and superimposed acquired mutations.
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PMID:Mitochondrial DNA polymorphism in substantia nigra. 899 25

The Pacific-rim, dioecious bivalve Mytilus californianus contains two distinct sequence types of mitochondrial (mt) DNA that are gender-limited in their occurrence. One type (F) is found in both females and males, but the second type (M) is strictly limited to males. Although F- and M-type mtDNAs occur in approximately equal proportion in testes, there is a preponderance of M-type in sperm. Segments of the COI and ND5 genes of F-type and M-type mtDNAs differ in nucleotide sequence by 21.1% and 31.6%, and in predicted amino-acid sequence by 7.9% and 27.1%, respectively. These latter observations raise hitherto unconsidered questions regarding the number of different variants of cytochrome c oxidase and NADH dehydrogenase that may occur in Mytilus non-gametic male cells.
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PMID:Gender-associated diverse mitochondrial DNA molecules of the mussel Mytilus californianus. 910 39

In parasitic kinetoplastid protozoa, mitochondrial (mt) mRNAs are post-transcriptionally edited by insertion and deletion of uridylate residues, the information being provided by guide (g) RNAs. In order to further explore the role and evolutionary history of this process, we searched for editing in mt RNAs of the free-living bodonid Bodo saltans. We found extensive editing in the transcript for NADH dehydrogenase (ND) subunit 5, which is unedited in trypanosomatids. In contrast, B.saltans cytochrome c oxidase (cox) subunit 2 and maxicircle unidentified reading frame (MURF) 2 RNAs display limited editing in the same regions as their trypanosomatid counterparts. A putative intramolecular cox2 gRNA and the gene for gMURF2-I directing the insertion of only one U in the 5' editing domain of MURF2 RNA, are conserved in B.saltans. This lends (further) evolutionary support to the proposed role of these sequences as gRNAs. Phylogenetic analysis showed that B.saltans is more closely related to trypanosomatids than the cryptobiids Trypanoplasma borreli and Cryptobia helicis, in line with the trypanosomatid-like cox2 and MURF2 RNA editing patterns. Nevertheless, other features like the apparent absence of a catenated mtDNA network, are shared with bodonid and cryptobiid species. ND5 RNA editing may represent yet another example of editing 'on the way out' during kinetoplastid evolution, but in view of the fact that cox2 RNA is unedited in T. borreli and C.helicis, we infer that the editing of this RNA may have arisen relatively recently. Our results provide the first examples of RNA editing in a free-living kinetoplastid, indicating that there is no direct link between U-insertion/deletion editing and a parasitic lifestyle.
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PMID:RNA editing in the free-living bodonid Bodo saltans. 946 17

The NADH-ubiquinone oxidoreductase (type I NDH) of Rhodobacter capsulatus is a multisubunit enzyme encoded by the 14 genes of the nuo operon. This bacterial enzyme constitutes a valuable model for the characterization of the mitochondrial Complex I structure and enzymatic mechanism for the following reasons. (i) The mitochondria-encoded ND subunits are not readily accessible to genetic manipulation. In contrast, the equivalents of the mitochondrial ND1, ND2, ND4, ND4L, ND5 and ND6 genes can be easily mutated in R. capsulatus by homologous recombination. (ii) As illustrated in the case of ND1 gene, point mutations associated with human cytopathies can be reproduced and studied in this model system. (iii) The R. capsulatus model also allows the recombinant manipulations of iron-sulfur (Fe-S) subunits and the assignment of Fe-S clusters as illustrated in the case of the NUOI subunit (the equivalent of the mitochondrial TYKY subunit). (iv) Finally, like mitochondrial Complex I, the NADH-ubiquinone oxidoreductase of R. capsulatus is highly sensitive to the inhibitor piericidin-A which is considered to bind to or close to the quinone binding site(s) of Complex I. Therefore, isolation of R. capsulatus mutants resistant to piericidin-A represents a straightforward way to map the inhibitor binding sites and to try and define the location of quinone binding site(s) in the enzyme. These illustrations that describe the interest in the R. capsulatus NADH-ubiquinone oxidoreductase model for the general study of Complex I will be critically developed in the present review.
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PMID:The complex I from Rhodobacter capsulatus. 959 68

The fix-2 mutant of Rhizobium meliloti affected in the invasion of alfalfa root nodules (Inf-/Fix-) is K+ sensitive and unable to adapt to alkaline pH in the presence of K+. Using directed Tn5 mutagenesis, we delimited a 6kb genomic region in which mutations resulted in both Inf-/Fix- and K+-sensitive phenotypes. In this DNA region, seven open reading frames (ORFs) were identified and the corresponding genes were designated phaA, B, C, D, E, F and G. The putative PhaABC proteins exhibit homology to the subunits of a Na+/H+ antiporter from an alkalophilic Bacillus strain. Moreover, PhaA and PhaD also show similarity to the ND5 and ND4 subunits of the proton-pumping NADH:ubiquinone oxidoreductase respectively. Computer analysis suggests that all seven proteins are highly hydrophobic with several possible transmembrane domains. Some of these domains were confirmed by generating active alkaline phosphatase fusions. Ion transport studies on phaA mutant cells revealed a defect in K+ efflux at alkaline pH after the addition of a membrane-permeable amine. These results suggest that the pha genes of R. meliloti encode for a novel type of K+ efflux system that is involved in pH adaptation and is required for the adaptation to the altered environment inside the plant.
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PMID:The pha gene cluster of Rhizobium meliloti involved in pH adaptation and symbiosis encodes a novel type of K+ efflux system. 968 Feb 1

Oxidants are important in the regulation of signal transduction and gene expression. Multiple classes of genes are transcriptionally activated by oxidants and are implicated in different phenotypic responses. In the present study, we performed differential mRNA display to elucidate genes that are induced or repressed after exposure of rat lung epithelial (RLE) cells to H2O2 or crocidolite asbestos, a pathogenic mineral that generates oxidants. After 8 or 24 hr of exposure, RNA was extracted, reverse transcribed, and amplified by polymerase chain reaction with degenerate primers to visualize alterations in gene expression. The seven clones obtained were sequenced and encoded the mitochondrial genes, NADH dehydrogenase subunits ND5 and ND6, and 16S ribosomal RNA. Evaluation of their expression by Northern blot analysis revealed increased expression of 16S rRNA after 1 or 2 hr of exposure to H2O2. At later time periods (4 and 24 hr), mRNA levels of 16S rRNA and NADH dehydrogenase were decreased in H2O2-treated RLE cells when compared to sham controls. Crocidolite asbestos caused increases in 16S rRNA levels after 8 hr of exposure, whereas after 24 hr of exposure to asbestos, 16S rRNA levels were decreased in comparison to sham controls. In addition to these oxidants, the nitric oxide generator spermine NONOate caused similar decreases in NADH dehydrogenase mRNA levels after 4 hr of exposure. The present data and previous studies demonstrated that all oxidants examined resulted in apoptosis in RLE cells during the time frame where alterations of mitochondrial gene expression were observed. As the mitochondrion is a major organelle that controls apoptosis, alterations in expression of mitochondrial genes may be involved in the regulation of apoptosis.
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PMID:Modulation of mitochondrial gene expression in pulmonary epithelial cells exposed to oxidants. 978 97

Identification of the progenitors of plants endemic to oceanic islands often is complicated by extreme morphological divergence between island and continental taxa. This is especially true for the Hawaiian Islands, which are 3,900 km from any continental source. We examine the origin of Hesperomannia, a genus of three species endemic to Hawaii that always have been placed in the tribe Mutisieae of the sunflower family. Phylogenetic analyses of representatives from all tribes in this family using the chloroplast gene ndhF (where ndhF is the ND5 protein of chloroplast NADH dehydrogenase) indicate that Hesperomannia belongs to the tribe Vernonieae. Phylogenetic comparisons within the Vernonieae using sequences of both ndhF and the internal transcribed spacer regions of nuclear ribosomal DNA reveal that Hesperomannia is sister to African species of Vernonia. Long-distance dispersal northeastward from Africa to southeast Asia and across the many Pacific Ocean island chains is the most likely explanation for this unusual biogeographic connection. The 17- to 26-million-year divergence time between African Vernonia and Hesperomannia estimated by the DNA sequences predates the age of the eight existing Hawaiian Islands. These estimates are consistent with an hypothesis that the progenitor of Hesperomannia arrived at one of the low islands of the Hawaiian-Emperor chain between the late Oligocene and mid-Miocene when these islands were above sea level. Subsequent to its arrival the southeast Pacific island chains served as steppingstones for dispersal to the existing Hawaiian Islands.
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PMID:Molecular evidence for an African origin of the Hawaiian endemic Hesperomannia (Asteraceae). 986 Sep 87


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