Cited by 110Iron Metabolism and DisordersNeurological diseases and metabolismNuclear Structure and Function

Regulation, mechanisms and proposed function of ferritin translocation to cell nuclei

Thompson, Khristy J., Fried, Michael G., Ye, Zheng, Boyer, Phillip, Connor, James R.·2002·Journal of Cell Science

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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Crossref · 10.1242/jcs.115.10.2165

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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.

    “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).”

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Authors
Thompson, K. J., Fried, M. G., Ye, Z., Boyer, P., & Connor, J. R.
Affiliations
Pennsylvania State University (US)
Venue
Journal of Cell Science
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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