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Release of iron from ferritin requires lysosomal activity
Abstract
How ferritin-Fe becomes available for cell functions is unknown. Our previous studies with rat hepatoma cells indicated ferritin had to be degraded to release its Fe. In these studies, we investigated whether this occurs in other cell types and whether lysosomes are required. Release of ferritin-Fe was induced with desferoxamine (DFO) in (59)Fe-preloaded hepatoma, Caco2, and erythroid K562 cells and measured by rocket immunoelectrophoresis and autoradiography. The half-lives for ferritin-(59)Fe and protein were parallel (23, 16, and 11 h for the hepatic, Caco2, and K562 cells, respectively). Co-treatment with 180 microM Fe, leupeptin, chymostatin, or chloroquine markedly decreased rates of ferritin-Fe release and ferritin degradation. Lactacystin had no effect except for a small one in erythroid cells. Fractionation of hepatoma cell lysates on iodixanol gradients showed rapid depletion of cytosolic ferritin by DFO treatment but no accumulation in lysosomes. We conclude that regardless of cell type, release of Fe from ferritin occurs mainly through lysosomal proteolysis.
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“These results are consistent with lysosome-mediated ferritin degradation in MEFs as previously reported [51], [54], [55].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [54]
In the citing paper
“Ferritinophagy, the process of ferritin being sequestered into autophagosomes and delivered to lysosomes for degradation, is important for liberating iron from ferritin and thus for maintaining cellular iron homeostasis [51], [53], [54], [55].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [54]
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Cited by
Sorted by citations
Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy
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“Exit of iron from ferritin may occur through gated pores or by autophagy and lysosomal degradation of ferritin (129, 240).”
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Metadata
- Authors
- Kidane, T. Z., Sauble, E., & Linder, M. C.
- Affiliations
- California State University, Fullerton (US)
- ORCID
- Linder, Maria C.
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2006-09
- Volume
- 291
- Issue
- 3
- Pages
- C445-C455
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2136891799
- Cited by
- 263
- References
- 51
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 17 · 2023: 13 · 2022: 12 · 2021: 17 · 2020: 13 · 2019: 10 · 2018: 16 · 2017: 16 · 2016: 12 · 2015: 12 · 2014: 17 · 2013: 13 · 2012: 9
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk053080-04)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-53080)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- ferritin, iron release, lysosomal proteolysis, deferoxamine, ferritin degradation, lysosomes, hepatoma cells, Caco-2 cells, iron metabolism, leupeptin, chymostatin, chloroquine, lactacystin
- MeSH terms
- Animals, Chloroquine, Deferoxamine, Ferritins, Humans, Immunoelectrophoresis, Iron, Leupeptins, Lysosomes, Oligopeptides, Peptide Hydrolases, Protease Inhibitors, Caco-2 Cells, K562 Cells, Enterocytes, Hepatocytes, Erythroid Cells, Rats
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