The DOI matches its Crossref record; 73 of the 74 references it cites were found in a registry or an index.
Regulation, mechanisms and proposed function of ferritin translocation to cell nuclei
Abstract
Ferritin is traditionally considered a cytoplasmic iron-storage protein,but recent reports indicate that it is also found in cell nuclei. Nuclear ferritin has been proposed to be involved in both the protection of DNA and the exacerbation of iron-induced oxidative damage to DNA. We demonstrate that H-rich ferritin is present in the nucleus of human astrocytoma tumor cells. To study the mechanism and regulation of ferritin translocation to the nucleus,we developed a cell culture model using SW1088 human astrocytoma cells. Changes in cellular iron levels, cytokine treatments and hydrogen peroxide exposure affected the distribution of ferritin between the cytosol and the nucleus. Ferritin enters the nucleus via active transport through the nuclear pore and does not require NLS-bearing cytosolic factors for transport. Furthermore, H-rich ferritin is preferred over L-rich ferritin for uptake into the nucleus. Whole cell crosslinking studies revealed that ferritin is associated with DNA. Ferritin protected DNA from iron-induced oxidative damage in both in vitro and in cell culture models. These results strongly suggest a novel role for ferritin in nuclear protection. This work should lead to novel characterization of ferritin functions in the context of genomic stability and may have unparalleled biological significance in terms of the accessibility of metals to DNA. The knowledge generated as a result of these studies will also improve our understanding of iron-induced damage of nuclear constituents.
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“Serum ferritin has been thought to reflect the iron stores in the body and to increase as a secreted byproduct of intracellular ferritin synthesis (250, 297).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [297]
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Ferritins: A family of molecules for iron storage, antioxidation and more
Arosio, P., Ingrassia, R., & Cavadini, P. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.09.004 · Cited by 886
Intracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526
Quintana, C., Bellefqih, S., Laval, J. Y., Guerquin‐Kern, J., Wu, T., Ávila, J., Ferrer, I., Arranz, R., & Patiño, C. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.11.001 · Cited by 297
Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer
Truffi, M., Fiandra, L., Sorrentino, L., Monieri, M., Corsi, F., & Mazzucchelli, S. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.03.002 · Cited by 277
The iron redox and hydrolysis chemistry of the ferritins
Bou‐Abdallah, F. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2010.03.021 · Cited by 250
Metadata
- Authors
- Thompson, K. J., Fried, M. G., Ye, Z., Boyer, P., & Connor, J. R.
- Affiliations
- Pennsylvania State University (US)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2002-05-15
- Volume
- 115
- Issue
- 10
- Pages
- 2165-2177
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2119605126
- Cited by
- 110
- References
- 74
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 8 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 6 · 2014: 7 · 2013: 5 · 2012: 2
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK054289, DK54289)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- ferritin, nuclear translocation, astrocytoma cells, DNA protection, oxidative DNA damage, genome stability, hydrogen peroxide, cytokines, metal-DNA binding
- MeSH terms
- Astrocytoma, Cell Nucleus, DNA, DNA Damage, Ferritins, Humans, Hydrogen Peroxide, Iron, Tumor Cells, Cultured, Cytokines, Active Transport, Cell Nucleus
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