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Tanit Guitart Daria Picchioni David Pi?eyro Lluís Ribas de Pouplana 《Nucleic acids research》2013,41(13):6595-6608
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. 相似文献
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Jan Piťha 《Cell and tissue research》1968,90(4):563-569
Summary Paneth cells of rabbit small intestine almost constantly contain inclusions of variable size which consist of two components. The first consists of cylindrical bodies formed by concentric or spiral dense lamellae. The second is formed by tubules with triple-layered walls which may be arranged in a hexagonal pattern. The density of arrangement of both components is variable. The structure of inclusions is discussed in relation to their composition and derivation and lipid or lipoprotein composition is assumed. 相似文献
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