ArticleHuman molecular genetics2008
Iron-dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 137 citations in OpenAlex.
- Epigenetic therapy for Friedreich ataxia.Annals of neurology · 2014Trial
- Pathological frataxin deficiency in mice causes tissue-specific alterations in iron homeostasis.iScience · 2026Article
- Altered Ca2+ responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes.Journal of cell science · 2025Article
- The Regulation of the Disease-Causing GeneCells · 2024Review
- Neurodegenerative Diseases: New Hopes and Perspectives.Current molecular medicine · 2024Review
- Role and mechanism of ferroptosis in neurological diseases.Molecular metabolism · 2022Review
- Mice harboring the FXN I151F pathological point mutation present decreased frataxin levels, a Friedreich ataxia-like phenotype, and mitochondrial alterations.Cellular and molecular life sciences : CMLS · 2022Article
- Recent Advances in the Elucidation of Frataxin Biochemical Function Open Novel Perspectives for the Treatment of Friedreich's Ataxia.Frontiers in neuroscience · 2022Review
- Mammalian mitochondrial iron-sulfur cluster biogenesis and transfer and related human diseases.Biophysics reports · 2021Article
- Cysteine Deprivation Targets Ovarian Clear Cell CarcinomaAntioxidants & redox signaling · 2020Article
- An Overview of the Ferroptosis Hallmarks in Friedreich's Ataxia.Biomolecules · 2020Review
- Review
- Analysis of Putative Epigenetic Regulatory Elements in theInternational journal of molecular sciences · 2020Review
- Outlining the Complex Pathway of Mammalian Fe-S Cluster Biogenesis.Trends in biochemical sciences · 2020Review
- Molecular Defects in Friedreich's Ataxia: Convergence of Oxidative Stress and Cytoskeletal Abnormalities.Frontiers in molecular biosciences · 2020Review
- Article
- Iron regulatory protein 2 modulates the switch from aerobic glycolysis to oxidative phosphorylation in mouse embryonic fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The role of mitochondrial labile iron in Friedreich's ataxia skin fibroblasts sensitivity to ultraviolet A.Metallomics : integrated biometal science · 2019Article
- Impact ofInternational journal of molecular sciences · 2018Review
- Acute loss of iron-sulfur clusters results in metabolic reprogramming and generation of lipid droplets in mammalian cells.The Journal of biological chemistry · 2018Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Friedreich ataxia (FA) is a progressive neurodegenerative disease caused by expansion of a trinucleotide repeat within the first intron of the gene that encodes frataxin. In our study, we investigated the regulation of frataxin expression by iron and demonstrated that frataxin mRNA levels decrease significantly in multiple human cell lines treated with the iron chelator, desferal (DFO). In addition, frataxin mRNA and protein levels decrease in fibroblast and lymphoblast cells derived from both normal controls and from patients with FA when treated with DFO. Lymphoblasts and fibroblasts of FA patients have evidence of cytosolic iron depletion, as indicated by increased levels of iron regulatory protein 2 (IRP2) and/or increased IRE-binding activity of IRP1. We postulate that this inferred cytosolic iron depletion occurs as frataxin-deficient cells overload their mitochondria with iron, a downstream regulatory effect that has been observed previously when mitochondrial iron-sulfur cluster assembly is disrupted. The mitochondrial iron overload and presumed cytosolic iron depletion potentially further compromise function in frataxin-deficient cells by decreasing frataxin expression. Thus, our results imply that therapeutic efforts should focus on an approach that combines iron removal from mitochondria with a treatment that increases cytosolic iron levels to maximize residual frataxin expression in FA patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.