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Specific iron chelators determine the route of ferritin degradation
Open accessAbstract
Deferoxamine (DFO) is a high-affinity Fe (III) chelator produced by Streptomyces pilosus. DFO is used clinically to remove iron from patients with iron overload disorders. Orally administered DFO cannot be absorbed, and therefore it must be injected. Here we show that DFO induces ferritin degradation in lysosomes through induction of autophagy. DFO-treated cells show cytosolic accumulation of LC3B, a critical protein involved in autophagosomal-lysosomal degradation. Treatment of cells with the oral iron chelators deferriprone and desferasirox did not show accumulation of LC3B, and degradation of ferritin occurred through the proteasome. Incubation of DFO-treated cells with 3-methyladenine, an autophagy inhibitor, resulted in degradation of ferritin by the proteasome. These results indicate that ferritin degradation occurs by 2 routes: a DFO-induced entry of ferritin into lysosomes and a cytosolic route in which iron is extracted from ferritin before degradation by the proteasome.
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In primary MEFs, Dfo (50 μM) stimulated ferritin degradation substantially within 6 h.
“Ferritin degradation was then stimulated with the iron chelator deferoxamine (Dfo) (50 µM) as previously described [51], [53], [56] and occurred substantially within 6 h of treatment (Fig. 5A(i)).”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [56]
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Metadata
- Authors
- De Domenico, I., Ward, D. M., & Kaplan, J.
- Affiliations
- Departments of Internal Medicine and
- University of Utah (US)
- ORCID
- Ward, Diane McVey
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-11-12
- Volume
- 114
- Issue
- 20
- Pages
- 4546-4551
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2777130
- OpenAlex
- W2062266319
- Cited by
- 176
- References
- 30
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 13 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 11 · 2018: 8 · 2017: 8 · 2016: 8 · 2015: 11 · 2014: 10 · 2013: 14 · 2012: 14
- FWCI
- 11.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McGill University
- National Institutes of Health (DK030534)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK070947, R01DK030534, R37DK030534, R01DK070947, DK030534)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- ferritin degradation, deferoxamine, iron chelators, autophagy, lysosomal degradation, proteasomal degradation, LC3B, iron overload
- MeSH terms
- Autophagy, Cells, Cultured, Cytosol, Deferoxamine, Ferritins, Fluorescent Antibody Technique, Humans, Iron Chelating Agents, Lysosomes, Siderophores, Proteasome Endopeptidase Complex
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