Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a unique Chinese hamster mutant, Gal-32, the mitochondrially encoded subunits of cytochrome c oxidase (CO I, II, III) and NADH dehydrogenase (ND 1-6) are greatly decreased while other mitochondrially synthesized proteins, such as ATPase subunits 6 and 8, are less affected. Pulse-chase experiments with [35S]methionine demonstrated that the reduced amounts of CO I and ND 5 subunits in Gal-32 are not the result of more rapid protein degradation. No differences in sizes of mtRNAs were detected between wild type and mutant using Northern blotting. The steady state levels of both heavy and light strand mtDNA transcripts were elevated in Gal-32: CO I mRNA was 1.5-fold higher in the mutant than in the wild type; ND 5 mRNA was 1.9-fold higher; ND 6 precursor RNAs were 1.4-fold higher and ATPase 6 and 8 mRNA (a single transcript) was 2.7-fold higher. Thus, the amounts of translation products are roughly correlated with the levels of mRNAs. The reduced levels of mitochondrially synthesized proteins in Gal-32 are the result of decreased translation of specific mRNAs, not increased degradation of mtRNAs.
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PMID:Elevated mitochondrial RNA in a Chinese hamster mutant deficient in the mitochondrially encoded subunits of NADH dehydrogenase and cytochrome c oxidase. 169 38

To determine whether a mitochondrial mRNA deficiency exists in mitochondrial myopathies, muscle biopsies from a patient with chronic progressive external ophthalmoplegia (CPEO) and a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) were studied using in situ hybridization. Histochemistry and immunohistochemistry were performed along with hybridization. Hybridization reactions were widely distributed over the sarcoplasm of all muscle fibers in the patient with MELAS. In the patient with CPEO, 80% of the fibers showed a marked decrease in density of autoradiographic grains. This marked decrease corresponded to the histochemical and immunohistochemical findings of a very weak staining of cytochrome c oxidase (CCO). The isotope-labeled cDNA probe used in in situ hybridization in this study complements a part of subunit I of CCO and a part of subunit II of complex I in the mitochondrial gene. Our results suggest a defect in the mRNA in this CPEO patient.
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PMID:In situ hybridization of muscle mitochondrial mRNA in mitochondrial myopathies. 170 73

Purified ubiquinol-cytochrome c reductase of beef heart mitochondria is very stable in aqueous solution; it suffers little damage upon illumination with visible light under aerobic or anaerobic conditions. However, it is rapidly inactivated when the photosensitizer hematoporphyrin is present during illumination. The hematoporphyrin-promoted photoactivation is dependent on sensitizer dose, illumination time, and oxygen. Singlet oxygen is shown to be the destructive agent in this system. The photoinactivation of ubiquinol-cytochrome c reductase is prevented by excess exogenous ubiquinone, regardless of its redox state. This protective effect is not due to protein-ubiquinone interactions but to the singlet oxygen scavenger property of ubiquinone. Ubiquinone also protects against hematoporphyrin-promoted photoinactivation of succinate-ubiquinone reductase and cytochrome c oxidase. The photoinactivation site in ubiquinol-cytochrome c reductase is the iron-sulfur cluster of Rieske's protein. Two histidine residues, presumably serving as two ligands for the iron-sulfur cluster of Rieske's protein, are destroyed. No polypeptide bond cleavage is detected. Photoinactivation has little effect on the spectral properties of cytochromes b and c1 but alters their reduction rates substantially. this photoinactivation also causes the formation of proton-leaking channels in the complex. When the photoinactivated reductase is co-inlaid with intact ubiquinol-cytochrome c reductase or cytochrome c oxidase in a phospholipid vesicle, no proton ejection can be detected during the oxidation of their corresponding substrates.
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PMID:Hematoporphyrin-promoted photoinactivation of mitochondrial ubiquinol-cytochrome c reductase: selective destruction of the histidine ligands of the iron-sulfur cluster and protective effect of ubiquinone. 184 89

Leigh's disease is one of the mitochondrial encephalomyopathies. This article presents a 7-month-old baby boy who had been well-being since birth until 6 months of age when episodic downward gaze of both eyes with limitation of horizontal eye movement were noted. This episode of cranial nerve palsies lasted about 4-5 days and subsided spontaneously. The second attack was noted one month later, to be associated with hypotonia and truncal ataxia. Episodic hyperventilation with resultant gasping and myoclonus was noted at the third attack but spontaneous respiration resumed soon with persistent ophthalmoplegia and truncal ataxia. Lumbar puncture, brain MRI, amino acid assay and cardiac echo all showed negative finding. The oral glucose lactate stimulation test revealed an elevation of lactic acid, brain stem evoked potential indicated bilateral obscure 4th and 5th waves, and muscle biopsy showed ragged red fibres with aggregation of structurally abnormal mitochondria noted under electron microscope. Coenzyme Q, thiamine and carnitine had been given before biochemical study; however, the neurological symptoms did not show any improvement. Biochemical study finally revealed normal respiratory chain enzymes including NADH-coenzyme Q reductase, succinate coenzyme Q reductase and cytochrome c oxidase while other enzymes were technically unavailable for study. Unfortunately the patient died at 18-month-old due to respiratory failure.
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PMID:Mitochondrial encephalomyopathy presenting with clinical Leigh's disease: report of a case. 184 64

Genetic, biochemical and morphological investigations were conducted on skeletal muscle mitochondria from 6 cases of ocular myopathy: 4 cases with Kearns-Sayre syndrome (KSS) and 2 with chronic progressive external ophthalmoplegia. All of these 6 cases showed mitochondrial DNA (mtDNA) deletions in addition to normal sized DNA in the quadriceps muscle. The deletions ranging from 3 to 8 kbp were also mapped between nucleotides 5500 and 16000 by Southern blot. The deleted genes encoded for some subunits of complexes I, IV, V and 5-10 tRNAS. The boundaries of the deletions have been sequenced in three patients. Five patients had mitochondrial respiratory chain deficiency in complex I as shown by the low oxygen consumption in isolated mitochondria using three NAD(+)-linked substrates. Mitochondria with an abnormal ultrastructure were also observed in 2 cases. A good relationship between the cytochrome c oxidase deficiency and the amount of deleted mtDNA was shown in our present investigations.
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PMID:Deletions of mitochondrial DNA in Kearns-Sayre syndrome and ocular myopathies: genetic, biochemical and morphological studies. 185 20

The effects of arachidonic acid on the enzyme complexes in the electron transport system were investigated using submitochondrial particles from rat brain. Arachidonic acid irreversibly inhibited NADH-CoQ oxidoreductase (complex I) activity, but had no effect on the activities of succinate-CoQ oxidoreductase (complex II), CoQH2-cytochrome c oxidoreductase (complex III), cytochrome c oxidase (complex IV), ATPase (complex V), glutamate dehydrogenase, and malate dehydrogenase up to 50 microM. The inhibition was dose-dependent with an IC50 value of 110 nmol/mg protein. The Lineweaver-Burk plot revealed that the inhibition by arachidonic acid was noncompetitive against CoQ with a Ki value of 33 microM and uncompetitive against NADH with a Ki value of 22 microM.
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PMID:Selective inhibition of NADH-CoQ oxidoreductase (complex I) of rat brain mitochondria by arachidonic acid. 190 30

A patient with chronic progressive external ophthalmoplegia (CPEO) who had abundant cytoplasmic bodies in muscle fibers and a deletion of mitochondrial DNA is reported. The patient was a 26-year-old male suffering from ophthalmoplegia from age 21. He had a marfanoid skeletal abnormality and perceptive hearing loss, but had neither retinopathy, ataxia, nor dementia. In the mitochondria isolated from the biopsied skeletal muscle, NADH-ubiquinone oxidoreductase activity was slightly decreased, succinate-cytochrome c reductase activity was slightly increased, and cytochrome c oxidase activity remained normal. Southern blot analysis of the muscle DNA identified heteroplasmy composed of a normal-sized mitochondrial DNA and a mutant mitochondrial DNA with a 4.2-kilobase deletion. The PCR plus S1 analysis showed that the deletion extended from nucleotide position 7860 +/- 60 to 12,090 +/- 70. The histological studies of the biopsied muscle revealed ragged-red fibers and cytochrome c oxidase-negative fibers in 15.7% and 18.6% of the muscle fibers, respectively. Other conspicuous histological change was abundant cytoplasmic bodies surrounded by clusters of abnormal mitochondria. The cytoplasmic bodies were found preferentially in type 1 fibers, and exclusively in cytochrome c oxidase-negative fibers and in ragged-red fibers. Focal existence of cytoplasmic bodies in muscle fibers with abnormal mitochondria suggests that segregated distribution of the abnormal mitochondria with deleted mitochondrial DNA is involved in the pathogenesis of cytoplasmic bodies.
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PMID:Cytoplasmic body and mitochondrial DNA deletion. 196 59

A 34-year-old man affected by exercise intolerance, mild proximal weakness and severe lactic acidosis is described. Muscle biopsy revealed mitochondrial abnormalities and an increase of cytochrome c oxidase histochemical reaction. Biochemical investigations on isolated muscle mitochondria as well as polarographic studies revealed a mitochondrial NADH-CoQ reductase (complex I) deficiency. Mitochondrial dysfunction was confirmed by 31P nuclear magnetic resonance spectroscopy. Immunological investigation showed a generalized reduction of all complex I polypeptides. Genetic analysis did not reveal mitochondrial DNA deletions. The biochemical defect was not present in the patient's muscle tissue culture. Metabolic measurements and functional evaluation showed a reduced mechanical efficiency during exercise.
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PMID:A case of mitochondrial myopathy, lactic acidosis and complex I deficiency. 212 37

The immunohistochemical reaction of monoclonal as well as polyclonal antibodies against cytochrome c oxidase (COX) subunits with serial sections of normal human skeletal muscle was investigated. The stronger reactivity of polyclonal antibodies to COX subunits II-III and VIIbc with type I as compared to type II fibres, correlated well with the higher histochemical reactivity of NADH dehydrogenase, succinate dehydrogenase and cytochrome c oxidase in type I fibres. In contrast an almost exclusive reaction of a monoclonal antibody against subunit IV with type I fibre and a preponderant reaction of a polyclonal antibody against subunits Vab with type II fibres was obtained. Antibodies against subunits I, Vb and VIc did not reveal a fibre-type-specific reactivity. The data indicate in human muscle the occurrence of fibre type-specific isozymes of cytochrome c oxidase differing in subunits IV and Va or Vb.
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PMID:Immunohistochemical demonstration of fibre type-specific isozymes of cytochrome c oxidase in human skeletal muscle. 216 12

Brain mitochondrial enzyme activities were examined in 15-day-old suckling mice which were daily injected with D-penicillamine (DP), a chelating agent of copper. Newborn mice treated with DP (1 g/kg/day) showed retarded weight gain, hyperelasticity of skin, and a bizarre forelimb posture with subcutaneous edema on experimental day (ED) 7. Paraparesis or dragging of the hindlimbs was observed by ED 15. Brain copper contents of DP-treated mice decreased to 34% of the controls of ED 15. Cytochrome c oxidase activity (complex IV) in the brain showed 51% decrease of the controls, on the contrary, rotenone-sensitive NADH cytochrome c reductase (complex I + III) and succinate cytochrome c reductase (complex II + III) were normal. Histochemistry of cytochrome c oxidase in the cerebellum of DP-treated mice disclosed diffuse reduction of staining, especially in Purkinje cells. These data show that DP-induced copper deficiency in the brain subsequently disturbs mitochondrial electron transport system, selectively cytochrome c oxidase activity. This seems to be a useful animal model not only for Menkes' kinky hair disease but also for mitochondrial encephalomyopathy.
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PMID:D-penicillamine-induced copper deficiency in suckling mice: neurological abnormalities and brain mitochondrial enzyme activities. 217 57


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