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Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels

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Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels

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dc.contributor.author Navarro Langa, Juan Antonio es_ES
dc.contributor.author Llorens Llorens, Jose Vte. es_ES
dc.contributor.author Soriano Rodríguez, Sirena es_ES
dc.contributor.author Botella, José A. es_ES
dc.contributor.author Schneuwly, Stephan es_ES
dc.contributor.author Martínez Sebastián, María José es_ES
dc.contributor.author Moltó Ruiz, María Dolores es_ES
dc.date.accessioned 2015-06-22T09:50:05Z
dc.date.available 2015-06-22T09:50:05Z
dc.date.issued 2011 es_ES
dc.identifier.citation PLoS ONE Vol. 6 Issue 7: es_ES
dc.identifier.uri http://hdl.handle.net/10550/44656
dc.description.abstract BackgroundFriedreich's ataxia (FA), the most frequent form of inherited ataxias in the Caucasian population, is caused by a reduced expression of frataxin, a highly conserved protein. Model organisms have contributed greatly in the efforts to decipher the function of frataxin; however, the precise function of this protein remains elusive. Overexpression studies are a useful approach to investigate the mechanistic actions of frataxin; however, the existing literature reports contradictory results. To further investigate the effect of frataxin overexpression, we analyzed the consequences of overexpressing human (FXN) and fly (FH) frataxins in Drosophila.Methodology/Principal FindingsWe obtained transgenic flies that overexpressed human or fly frataxins in a general pattern and in different tissues using the UAS-GAL4 system. For both frataxins, we observed deleterious effects at the biochemical, histological and behavioral levels. Oxidative stress is a relevant factor in the frataxin overexpression phenotypes. Systemic frataxin overexpression reduces Drosophila viability and impairs the normal embryonic development of muscle and the peripheral nervous system. A reduction in the level of aconitase activity and a decrease in the level of NDUF3 were also observed in the transgenic flies that overexpressed frataxin. Frataxin overexpression in the nervous system reduces life span, impairs locomotor ability and causes brain degeneration. Frataxin aggregation and a misfolding of this protein have been shown not to be the mechanism that is responsible for the phenotypes that have been observed. Nevertheless, the expression of human frataxin rescues the aconitase activity in the fh knockdown mutant.Conclusion/SignificanceOur results provide in vivo evidence of a functional equivalence for human and fly frataxins and indicate that the control of frataxin expression is important for treatments that aim to increase frataxin levels. es_ES
dc.title Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels es_ES
dc.type journal article es_ES
dc.identifier.doi 10.1371/journal.pone.0021017 es_ES
dc.identifier.idgrec 068987 es_ES

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