ArticlePloS one2011
Overexpression of human and fly frataxins in Drosophila provokes deleterious effects at biochemical, physiological and developmental levels.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Molecular evolution in light of regulatory-coding epistasis.EMBO reports · 2026Review
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- Wings of Discovery: UsingCells · 2025Review
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- Posttranslational regulation of mitochondrial frataxin and identification of compounds that increase frataxin levels in Friedreich's ataxia.The Journal of biological chemistry · 2022Article
- Recent Advances in the Elucidation of Frataxin Biochemical Function Open Novel Perspectives for the Treatment of Friedreich's Ataxia.Frontiers in neuroscience · 2022Review
- Advantages and Limitations of Gene Therapy and Gene Editing for Friedreich's Ataxia.Frontiers in genome editing · 2022Review
- High Levels of Frataxin Overexpression Lead to Mitochondrial and Cardiac Toxicity in Mouse Models.Molecular therapy. Methods & clinical development · 2020Article
- Effect of Mitochondrial and Cytosolic FXN Isoform Expression on Mitochondrial Dynamics and Metabolism.International journal of molecular sciences · 2020Article
- Defining Transcription Regulatory Elements in the Human Frataxin Gene: Implications for Gene Therapy.Human gene therapy · 2020Article
- CRISPR-Cas9 Gene Editing of Hematopoietic Stem Cells from Patients with Friedreich's Ataxia.Molecular therapy. Methods & clinical development · 2020Article
- Analysis of Putative Epigenetic Regulatory Elements in theInternational journal of molecular sciences · 2020Review
- A new tool to determine the cellular metabolic landscape: nanotechnology to the study of Friedreich's ataxia.Scientific reports · 2019Article
- Impact ofInternational journal of molecular sciences · 2018Review
- Adding a temporal dimension to the study of Friedreich's ataxia: the effect of frataxin overexpression in a human cell model.Disease models & mechanisms · 2018Article
- Expression of the Shrimp wap gene in Drosophila elicits defense responses and protease inhibitory activity.Scientific reports · 2018Article
- Frataxin overexpression in Müller cells protects retinal ganglion cells in a mouse model of ischemia/reperfusion injury in vivo.Scientific reports · 2018Article
- Review
- Iron Sulfur and Molybdenum Cofactor Enzymes Regulate theFrontiers in physiology · 2018Article
- Mitofusin-Dependent ER Stress Triggers Glial Dysfunction and Nervous System Degeneration in aFrontiers in molecular neuroscience · 2018Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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/SIGNIFICANCE: Our 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.
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