Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I
| Autor: | Michele Minuto, Nazzareno Capitanio, Massimo Zeviani, Sergio Papa, Claudia Piccoli, Arcangela Iuso, Raffaella Trentadue, Maria Ripoli, Vittoria Petruzzella, Salvatore Scacco, Francesco Bellomo |
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| Rok vydání: | 2006 |
| Předmět: |
Transcription
Genetic Mutant Mitochondrion medicine.disease_cause NADPH Oxidoreductases Biochemistry Antioxidants Membrane Potentials Adenosine Triphosphate Cyclic AMP Electrophoresis Gel Two-Dimensional NADH NADPH Oxidoreductases Catalysis Cell Line Cell Respiration Codon Nonsense Electron Transport Electron Transport Complex I Electrophoresis Polyacrylamide Gel Fibroblasts Glutathione Homozygote Humans Hydrogen Peroxide Kinetics Microscopy Confocal Mitochondria NADH Dehydrogenase Oxygen Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction Mutation chemistry.chemical_classification Gel Microscopy NDUFS1 Glutathione peroxidase NDUFS4 Confocal Two-Dimensional Transcription Electrophoresis Nonsense mutation Biology Genetic medicine Codon Molecular Biology Reactive oxygen species Polyacrylamide Gel Cell Biology Molecular biology Nonsense chemistry NADH |
| Zdroj: | 281 (2006): 10374–10380. info:cnr-pdr/source/autori:Iuso A, Scacco S, Piccoli C, Bellomo F, Petruzzella V, Trentadue R, Minuto M, Ripoli M, Capitanio N, Zeviani M, Papa S./titolo:Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I/doi:/rivista:/anno:2006/pagina_da:10374/pagina_a:10380/intervallo_pagine:10374–10380/volume:281 |
| Popis: | The pathogenic mechanism of a G44A nonsense mutation in the NDUFS4 gene and a C1564A mutation in the NDUFS1 gene of respiratory chain complex I was investigated in fibroblasts from human patients. As previously observed the NDUFS4 mutation prevented complete assembly of the complex and caused full suppression of the activity. The mutation (Q522K replacement) in NDUFS1 gene, coding for the 75-kDa Fe-S subunit of the complex, was associated with (a) reduced level of the mature complex, (b) marked, albeit not complete, inhibition of the activity, (c) accumulation of H(2)O(2) and O(2)(.-) in mitochondria, (d) decreased cellular content of glutathione, (e) enhanced expression and activity of glutathione peroxidase, and (f) decrease of the mitochondrial potential and enhanced mitochondrial susceptibility to reactive oxygen species (ROS) damage. No ROS increase was observed in the NDUFS4 mutation. Exposure of the NDUFS1 mutant fibroblasts to dibutyryl-cAMP stimulated the residual NADH-ubiquinone oxidoreductase activity, induced disappearance of ROS, and restored the mitochondrial potential. These are relevant observations for a possible therapeutical strategy in NDUFS1 mutant patients. |
| Databáze: | OpenAIRE |
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