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)

It is known that respiratory function deteriorates with age. Endogenous damage to DNA is thought to contribute to the aging process. The mitochondrial oxidative phosphorylation system, a bio-engine, consists of five complexes, and 13 subunits of those complexes are biosynthesized from information encoded in mitochondrial DNA. Mitochondrial DNA is shown to have a much higher mutation rate than nuclear DNA. We examined the diaphragms obtained at autopsy from 34 humans, 23 men and 11 women, ranging in age from 25 to 85 yr, for mitochondrial DNA deletions using the polymerase chain reaction method. Multiple mitochondrial DNA deletions were detected particularly among the elderly; the number of deletions in those over age 70 was significantly higher than in those under age 40. The occurrence of a 3.4-kbp deletion of mitochondrial DNA increased with age, i.e., 0% of those under age 30, 20.0% of those in their forties, 25.0% of those in their fifties, 28.6% of those in their sixties, 72.7% of those in their seventies, and in all of those over age 80. The mutation was based on the directly repeated sequence, 5'-TCACCCC-3', which exists in both the CO3 gene and the ND5 gene. Replication impairment occurred at that directly repeated sequence, which caused the elimination of a genome between the CO3 gene and the ND5 gene, and information for biosynthesis of four subunits in complex I (ND3, ND4L, ND4, and ND5), one in complex IV (CO3), and five transfer RNA genes was missing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aging-associated deletions of human diaphragmatic mitochondrial DNA. 158 Oct 77

We have cloned and sequenced over 9 kb of the mitochondrial genome from the sea star Pisaster ochraceus. Within a continuous 8.0-kb fragment are located the genes for NADH dehydrogenase subunits 1, 2, 3, and 4L (ND1, ND2, ND3, and ND4L), cytochrome oxidase subunits I, II, and III (COI, COII, and COIII), and adenosine triphosphatase subunits 6 and 8 (ATPase 6 and ATPase 8). This large fragment also contains a cluster of 13 tRNA genes between ND1 and COI as well as the genes for isoleucine tRNA between ND1 and ND2, arginine tRNA between COI and ND4L, lysine tRNA between COII and ATPase 8, and the serine (UCN) tRNA between COIII and ND3. The genes for the other five tRNAs lie outside this fragment. The gene for phenylalanine tRNA is located between cytochrome b and the 12S ribosomal genes. The genes for tRNA(glu) and tRNA(thr) are 3' to 12S ribosomal gene. The tRNAs for histidine and serine (AGN) are adjacent to each other and lie between ND4 and ND5. These data confirm the novel gene order in mitochondrial DNA (mtDNA) of sea stars and delineate additional distinctions between the sea star and other mtDNA molecules.
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PMID:Nucleotide sequence of nine protein-coding genes and 22 tRNAs in the mitochondrial DNA of the sea star Pisaster ochraceus. 197 16

Introduction of the constitutively active calcineurin gene into neonatal rat cardiomyocytes by adenovirus resulted in decreased mitochondrial membrane potential (P < 0.05). Infection of H9c2 cells with calcineurin adenovirus resulted in increased superoxide production (P < 0.001). Transgenic mice with cardiac-specific expression of a constitutively active calcineurin cDNA (CalTG mice) exhibit a two- to threefold increase in heart size that progresses to heart failure. We prepared mitochondria enriched for the subsarcolemmal population from the hearts of CalTG mice and transgene negative littermates (control). Intact, well-coupled mitochondria prepared from one to two mouse hearts at a time yielded sufficient material for functional studies. Mitochondrial oxygen consumption was measured with a Clark-type oxygen electrode with substrates for mitochondrial complex II (succinate) and complex IV [tetramethylpentadecane (TMPD)/ascorbate]. CalTG mice exhibited a maximal rate of electron transfer in heart mitochondria that was reduced by approximately 50% (P < 0.002) without a loss of respiratory control. Mitochondrial respiration was unaffected in tropomodulin-overexpressing transgenic mice, another model of cardiomyopathy. Western blotting for mitochondrial electron transfer subunits from mitochondria of CalTG mice revealed a 20-30% reduction in subunit 3 of complex I (ND3) and subunits I and IV of cytochrome oxidase (CO-I, CO-IV) when normalized to total mitochondrial protein or to the adenine nucleotide transporter (ANT) and compared with littermate controls (P < 0.002). Impaired mitochondrial electron transport was associated with high levels of superoxide production in the CalTG mice. Taken together, these data indicate that calcineurin signaling affects mitochondrial energetics and superoxide production. The excessive production of superoxide may contribute to the development of cardiac failure.
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PMID:Calcineurin transgenic mice have mitochondrial dysfunction and elevated superoxide production. 1239 29

Kinetoplast maxicircle DNA sequence organisation was investigated in Leishmania donovani, strain 1S LdBob. Gene arrangement in the coding (conserved) region of the maxicircle is collinear with that of most trypanosomatids, with individual genes showing 80-90% nucleotide identity to Leishmania tarentolae, strain UC. The notable exception was an integration of a full-size minicircle sequence in the ND1 gene coding region found in L. donovani. Editing patterns of the mitochondrial mRNAs investigated also followed L. tarentolae UC patterns, including productive editing of the components of respiratory complexes III-V, and ribosomal protein S12 (RPS12), as well as the lack of productive editing in five out of six pan-edited cryptogenes (ND3, ND8, ND9, G3, G4) found in these species. Several guide RNAs for the editing events were localised in minicircles and maxicircles in the locations that are conserved between the species. Mitochondrial activity, including rates of oxygen consumption, the presence and the levels of respiratory complexes and their individual subunits and the steady-state levels of several mitochondrial-encoded mRNAs were essentially the same in axenically grown amastigotes and in promastigotes of L. donovani. However, some modulation of mitochondrial activity between these developmental stages was suggested by the finding of an amastigote-specific component in complex IV, a down-regulation of mitochondrial RNA-binding proteins (MRP) and MRP-associated protein (MRP-AP) in amastigotes, and by variations in the levels of RPS12, ND3, ND9, G3 and G4 pre-edited transcripts.
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PMID:RNA editing and mitochondrial activity in promastigotes and amastigotes of Leishmania donovani. 1910 64

Cell respiration is controlled by nitric oxide (NO) reacting with respiratory chain complexes, particularly with Complex I and IV. The functional implication of these reactions is different owing to involvement of different mechanisms. Inhibition of complex IV is rapid (milliseconds) and reversible, and occurs at nanomolar NO concentrations, whereas inhibition of complex I occurs after a prolonged exposure to higher NO concentrations. The inhibition of Complex I involves the reversible S-nitrosation of a key cysteine residue on the ND3 subunit. The reaction of NO with cytochrome c oxidase (CcOX) directly involves the active site of the enzyme: two mechanisms have been described leading to formation of either a relatively stable nitrosyl-derivative (CcOX-NO) or a more labile nitrite-derivative (CcOX-NO (2) (-) ). Both adducts are inhibited, though with different K(I); one mechanism prevails on the other depending on the turnover conditions and availability of substrates, cytochrome c and O(2). SH-SY5Y neuroblastoma cells or lymphoid cells, cultured under standard O(2) tension, proved to follow the mechanism leading to degradation of NO to nitrite. Formation of CcOX-NO occurred upon rising the electron flux level at this site, artificially or in the presence of higher amounts of endogenous reduced cytochrome c. Taken together, the observations suggest that the expression level of mitochondrial cytochrome c may be crucial to determine the respiratory chain NO inhibition pathway prevailing in vivo under nitrosative stress conditions. The putative patho-physiological relevance of the interaction between NO and the respiratory complexes is addressed.
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PMID:Mitochondria and nitric oxide: chemistry and pathophysiology. 2239 19

This study investigated the genetic and enzymological features of Leigh syndrome due to respiratory chain complex deficiency in Chinese patients. The clinical features of 75 patients were recorded. Mitochondrial respiratory chain enzyme activities were determined via spectrophotometry. Mitochondrial gene sequence analysis was performed in 23 patients. Five core pedigrees were investigated via restriction fragment length polymorphism and gene sequencing. Psychomotor retardation (55%), motor regression (20%), weakness (29%), and epilepsy (25%) were the most frequent manifestations. Sixty-four patients (85.3%) had isolated respiratory complex deficiencies: complex I was seen in 28 patients (37.3%); complex II, seven (9.3%); complex III, six (8%); complex IV, ten (13.3%); and complex V, 13 patients (17.3%). Eleven patients (14.7%) had combined complex deficiencies. Mitochondrial DNA mutations were detected in 10 patients. Eight point mutations were found in mitochondrial structural genes: m.4833A>G in ND2, m.10191T>C in ND3, m.12338T>C and m.13513G>A in ND5, m.14502T>C and m.14487T>C in ND6, m.8108A>G in COXII, and m.8993T>G in ATPase6. Three mutations were found in tRNA genes: m.4395A>G in tRNA-Gln, m.10454T>C in tRNA-Arg, and m.5587T>C in tRNA-Ala. One patient and their mother both had the m.12338T>C and m.8993T>C mutations. In conclusion, mitochondrial respiratory chain complex I deficiency and structural gene mutations frequently occur in Chinese Leigh syndrome patients.
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PMID:Genetic and biochemical findings in Chinese children with Leigh syndrome. 2395 30

The Fas-activated serine/threonine kinase (FASTK) family of proteins has recently emerged as a central regulator of mitochondrial gene expression through the function of an unusual RNA-binding domain named RAP (for RNA-binding domain abundant in Apicomplexans), shared by all six members of the family. Here we describe the role of one of the less characterized members, FASTKD3, in mitochondrial RNA metabolism. First, we show that, in contrast to FASTK, FASTKD2, and FASTKD5, FASTKD3 does not localize in mitochondrial RNA granules, which are sites of processing and maturation of mtRNAs and ribosome biogenesis. Second, we generated FASTKD3 homozygous knock-out cell lines by homologous recombination and observed that the absence of FASTKD3 resulted in increased steady-state levels and half-lives of a subset of mature mitochondrial mRNAs: ND2, ND3, CYTB, COX2, and ATP8/6. No aberrant processing of RNA precursors was observed. Rescue experiments demonstrated that RAP domain is required for FASTKD3 function in mRNA stability. Besides, we describe that FASTKD3 is required for efficient COX1 mRNA translation without altering mRNA levels, which results in a decrease in the steady-state levels of COX1 protein. This finding is associated with reduced mitochondrial complex IV assembly and activity. Our observations suggest that the function of this family of proteins goes beyond RNA processing and ribosome assembly and includes RNA stability and translation regulation within mitochondria.
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PMID:Role of FAST Kinase Domains 3 (FASTKD3) in Post-transcriptional Regulation of Mitochondrial Gene Expression. 2778 13

DNA barcoding is a useful tool for documenting the diversity of metazoans. The most commonly used barcode markers, 16S and COI, are not considered suitable for species identification within some "basal" phyla of metazoans. Nevertheless metabarcoding studies of bulk mixed samples commonly use these markers and may obtain sequences for "basal" phyla. We sequenced mitochondrial DNA fragments of cytochrome oxidase c subunit I (COI), 16S ribosomal RNA (16S), NADH dehydrogenase subunits 2 (16S-ND2), 6 (ND6-ND3) and 4L (ND4L-MSH) for 27 species of Caribbean octocorals to create a reference barcode dataset and to compare the utility of COI and 16S to other markers more typically used for octocorals. The most common genera (Erythropodium, Ellisella, Briareum, Plexaurella, Muriceopsis and Pterogorgia) were effectively distinguished by small differences (5 or more substitutions or indels) in COI and 16S sequences. Gorgonia and Antillogorgia were effectively distinguished from each other by unique haplotypes, but the small genetic differences make distance approaches ineffective for these taxa. Plexaura, Pseudoplexaura and Eunicea were indistinguishable from each other but were generally effectively distinguished from other genera, further supporting the idea that these genera have undergone a rapid endemic radiation in the Caribbean.
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PMID:Reference DNA barcodes and other mitochondrial markers for identifying Caribbean Octocorals. 3082 53

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