Guitart 2013 Nucleic Acids Res: Difference between revisions
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{{Publication | {{Publication | ||
|title=Guitart T, Picchioni D, PiΓ±eyro D, Ribas de Pouplana L (2013) Human mitochondrial disease-like symptoms caused by a reduced tRNA aminoacylation activity in flies. Nucleic Acids Res 41:6595-608. Β | |title=Guitart T, Picchioni D, PiΓ±eyro D, Ribas de Pouplana L (2013) Human mitochondrial disease-like symptoms caused by a reduced tRNA aminoacylation activity in flies. Nucleic Acids Res 41:6595-608. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/23677612 PMID: 23677612 Open Access] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/23677612 PMID: 23677612 Open Access] | ||
|authors=Guitart T, Picchioni D, Pineyro D, Ribas de Pouplana L | |authors=Guitart T, Picchioni D, Pineyro D, Ribas de Pouplana L | ||
|year=2013 | |year=2013 | ||
|journal=Nucleic Acids Res | |journal=Nucleic Acids Res | ||
|abstract=The translation of genes encoded in the mitochondrial genome requires specific machinery that functions in the organelle. Among the many mutations linked to human disease that affect mitochondrial translation, several are localized to nuclear genes coding for mitochondrial aminoacyl-transfer RNA synthetases. The molecular significance of these mutations is poorly understood, but it is expected to be similar to that of the mutations affecting mitochondrial transfer RNAs. To better understand the molecular features of diseases caused by these mutations, and to improve their diagnosis and therapeutics, we have constructed a Drosophila melanogaster model disrupting the mitochondrial seryl-tRNA synthetase by RNA interference. At the molecular level, the knockdown generates a reduction in transfer RNA serylation, which correlates with the severity of the phenotype observed. The silencing compromises viability, longevity, motility and tissue development. At the cellular level, the knockdown alters mitochondrial morphology, biogenesis and function, and induces lactic acidosis and reactive oxygen species accumulation. We report that administration of antioxidant compounds has a palliative effect of some of these phenotypes. In conclusion, the fly model generated in this work reproduces typical characteristics of pathologies caused by mutations in the mitochondrial aminoacylation system, and can be useful to assess therapeutic approaches. Β | |abstract=The translation of genes encoded in the mitochondrial genome requires specific machinery that functions in the organelle. Among the many mutations linked to human disease that affect mitochondrial translation, several are localized to nuclear genes coding for mitochondrial aminoacyl-transfer RNA synthetases. The molecular significance of these mutations is poorly understood, but it is expected to be similar to that of the mutations affecting mitochondrial transfer RNAs. To better understand the molecular features of diseases caused by these mutations, and to improve their diagnosis and therapeutics, we have constructed a Drosophila melanogaster model disrupting the mitochondrial seryl-tRNA synthetase by RNA interference. At the molecular level, the knockdown generates a reduction in transfer RNA serylation, which correlates with the severity of the phenotype observed. The silencing compromises viability, longevity, motility and tissue development. At the cellular level, the knockdown alters mitochondrial morphology, biogenesis and function, and induces lactic acidosis and reactive oxygen species accumulation. We report that administration of antioxidant compounds has a palliative effect of some of these phenotypes. In conclusion, the fly model generated in this work reproduces typical characteristics of pathologies caused by mutations in the mitochondrial aminoacylation system, and can be useful to assess therapeutic approaches. | ||
|keywords=Aminoacyl-transfer RNA synthetases | |keywords=Aminoacyl-transfer RNA synthetases | ||
}} | }} | ||
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|topics=Coupling efficiency;uncoupling | |topics=Coupling efficiency;uncoupling | ||
|couplingstates=LEAK, OXPHOS | |couplingstates=LEAK, OXPHOS | ||
| | |pathways=N | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} |
Revision as of 17:13, 7 November 2016
Guitart T, Picchioni D, PiΓ±eyro D, Ribas de Pouplana L (2013) Human mitochondrial disease-like symptoms caused by a reduced tRNA aminoacylation activity in flies. Nucleic Acids Res 41:6595-608. |
Guitart T, Picchioni D, Pineyro D, Ribas de Pouplana L (2013) Nucleic Acids Res
Abstract: The translation of genes encoded in the mitochondrial genome requires specific machinery that functions in the organelle. Among the many mutations linked to human disease that affect mitochondrial translation, several are localized to nuclear genes coding for mitochondrial aminoacyl-transfer RNA synthetases. The molecular significance of these mutations is poorly understood, but it is expected to be similar to that of the mutations affecting mitochondrial transfer RNAs. To better understand the molecular features of diseases caused by these mutations, and to improve their diagnosis and therapeutics, we have constructed a Drosophila melanogaster model disrupting the mitochondrial seryl-tRNA synthetase by RNA interference. At the molecular level, the knockdown generates a reduction in transfer RNA serylation, which correlates with the severity of the phenotype observed. The silencing compromises viability, longevity, motility and tissue development. At the cellular level, the knockdown alters mitochondrial morphology, biogenesis and function, and induces lactic acidosis and reactive oxygen species accumulation. We report that administration of antioxidant compounds has a palliative effect of some of these phenotypes. In conclusion, the fly model generated in this work reproduces typical characteristics of pathologies caused by mutations in the mitochondrial aminoacylation system, and can be useful to assess therapeutic approaches. β’ Keywords: Aminoacyl-transfer RNA synthetases
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, mtDNA;mt-genetics, Genetic knockout;overexpression
Pathology: Aging;senescence, Inherited
Stress:Oxidative stress;RONS
Organism: Drosophila
Preparation: Permeabilized tissue
Regulation: Coupling efficiency;uncoupling Coupling state: LEAK, OXPHOS Pathway: N HRR: Oxygraph-2k