Human mitochondrial disease-like symptoms caused by a reduced tRNA aminoacylation activity in flies
Language: 
English
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.

Author(s): 
Guitart, Tanit
Picchioni, Daria
PiÒeyro, David
Ribas de Pouplana, LluÌs
Item Type: 
Journal Article
Publication Title: 
Nucleic Acids Research
Journal Abbreviation: 
Nucleic Acids Res.
Publication Date: 
2013-07
Publication Year: 
2013
Pages: 
6595-6608
Volume: 
41
Issue: 
13
ISSN: 
1362-4962
DOI: 
10.1093/nar/gkt402
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23677612 PMCID: PMC3711456

Turabian/Chicago Citation

Tanit Guitart, Daria Picchioni, David PiÒeyro and LluÌs Ribas de Pouplana. 2013-07. "Human mitochondrial disease-like symptoms caused by a reduced tRNA aminoacylation activity in flies." Nucleic Acids Research 41: 13: 6595-6608. 10.1093/nar/gkt402.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/nar/gkt402 | issn = 1362-4962 | volume = 41 | pages = 6595-6608 | last = Guitart | first = Tanit | coauthors = Picchioni, Daria, PiÒeyro, David, Ribas de Pouplana, LluÌs | title = Human mitochondrial disease-like symptoms caused by a reduced tRNA aminoacylation activity in flies | journal = Nucleic Acids Research | date = 2013-07 | pmid = | pmc = }} </ref>