ArticleHaematologica2011
Over-expression of mitochondrial ferritin affects the JAK2/STAT5 pathway in K562 cells and causes mitochondrial iron accumulation.
Article in Haematologica, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Review
- A novel view of ferritin in cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Vitamin B5 and succinyl-CoA improve ineffective erythropoiesis inScience translational medicine · 2023Article
- Review
- Neuronal Ablation of CoA Synthase Causes Motor Deficits, Iron Dyshomeostasis, and Mitochondrial Dysfunctions in a CoPAN Mouse Model.International journal of molecular sciences · 2020Article
- Fractalkine Induces Hepcidin Expression of BV-2 Microglia and Causes Iron Accumulation in SH-SY5Y Cells.Cellular and molecular neurobiology · 2019Article
- Pantothenate Rescues Iron Accumulation in Pantothenate Kinase-Associated Neurodegeneration Depending on the Type of Mutation.Molecular neurobiology · 2019Article
- Prognostic Value of Ferritin-to-Hemoglobin Ratio in Patients with Advanced Non-Small-Cell Lung Cancer.Journal of Cancer · 2019Article
- [Effect of iron chelation therapy on EPO-Stat5 signaling pathway and Treg expression in IPSS low risk/medium risk-1 group myelodysplastic syndrome patients].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2018Article
- Mitochondrial Ferritin Protects Hydrogen Peroxide-Induced Neuronal Cell Damage.Aging and disease · 2017Article
- A specialized pathway for erythroid iron delivery through lysosomal trafficking of transferrin receptor 2.Blood advances · 2017Article
- Coenzyme A corrects pathological defects in human neurons of PANK2-associated neurodegeneration.EMBO molecular medicine · 2016Article
- Ferritin heavy chain is a negative regulator of ovarian cancer stem cell expansion and epithelial to mesenchymal transition.Oncotarget · 2016Article
- Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control.Scientific reports · 2016Article
- Differences in vulnerability of neurons and astrocytes to heme oxygenase-1 modulation: Implications for mitochondrial ferritin.Scientific reports · 2016Article
- Mitochondrial iron and energetic dysfunction distinguish fibroblasts and induced neurons from pantothenate kinase-associated neurodegeneration patients.Neurobiology of disease · 2015Article
- Oxidative stress and the homeodynamics of iron metabolism.Biomolecules · 2015Review
- Mice lacking mitochondrial ferritin are more sensitive to doxorubicin-mediated cardiotoxicity.Journal of molecular medicine (Berlin, Germany) · 2014Article
- Fixing frataxin: 'ironing out' the metabolic defect in Friedreich's ataxia.British journal of pharmacology · 2014Review
- The iron metallome in eukaryotic organisms.Metal ions in life sciences · 2013Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMitochondrial ferritin is a nuclear encoded iron-storage protein localized in mitochondria. It has anti-oxidant properties related to its ferroxidase activity, and it is able to sequester iron avidly into the organelle. The protein has a tissue-specific pattern of expression and is also highly expressed in sideroblasts of patients affected by hereditary sideroblastic anemia and by refractory anemia with ringed sideroblasts. The present study examined whether mitochondrial ferritin has a role in the pathogenesis of these diseases. DESIGN AND
methodsWe analyzed the effect of mitochondrial ferritin over-expression on the JAK2/STAT5 pathway, on iron metabolism and on heme synthesis in erythroleukemic cell lines. Furthermore its effect on apoptosis was evaluated on human erythroid progenitors.
resultsData revealed that a high level of mitochondrial ferritin reduced reactive oxygen species and Stat5 phosphorylation while promoting mitochondrial iron loading and cytosolic iron starvation. The decline of Stat5 phosphorylation induced a decrease of the level of anti-apoptotic Bcl-xL transcript compared to that in control cells; however, transferrin receptor 1 transcript increased due to the activation of the iron responsive element/iron regulatory protein machinery. Also, high expression of mitochondrial ferritin increased apoptosis, limited heme synthesis and promoted the formation of Perls-positive granules, identified by electron microscopy as iron granules in mitochondria.
conclusionsOur results provide evidence suggesting that Stat5-dependent transcriptional regulation is displaced by strong cytosolic iron starvation status induced by mitochondrial ferritin. The protein interferes with JAK2/STAT5 pathways and with the mechanism of mitochondrial iron accumulation.
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