Characterization of nuclear ferritin and mechanism of translocation
Open accessAbstract
Ferritin, normally considered a cytoplasmic iron-storage protein, is also found in cell nuclei. It is an established fact that H-ferritin is the major form of nuclear ferritin, but little is known about the roles of ferritin in nuclei or about the mechanisms that control its appearance within the nuclear volume. In the present study, we show that, for human SW1088 astrocytoma cells, the nuclear and cytoplasmic forms of H-ferritin are products of the same mRNA. Histochemical and biochemical evidence is presented showing that ferritin is distributed non-randomly within the nuclear volume and that it preferentially associates with heterochromatin. Both cytoplasmic and nuclear populations of H-ferritin contain mixtures of non- and O-glycosylated forms, but the nuclear population is enriched in O-glycosylated forms. Cells treated with alloxan, a potent inhibitor of O-glycosylation, contained significantly less nuclear ferritin compared with cells grown in control media. Alloxan inhibited the reappearance of H-ferritin in nuclei of cells released from conditions of iron depletion, but did not prevent its disappearance from nuclei of cells undergoing iron depletion. These results suggest that O-glycosylation accompanies the transfer of ferritin from the cytoplasm to the nucleus, but does not influence the reverse process. The picture that emerges is one in which ferritin translocation between the cytoplasm and the nucleus is post-translationally regulated and responds to environmental and nutritional cues.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Decreased ferritin H expression was observed in Nrf2-knockout mice.
“decreased ferritin H expression was observed in Nrf2-knockout mice (290).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [290]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104 · see citing works
Colowick, S. P., Joshi, M. D., Jagannathan, & KAPLAN, N. O. (1966) · Cited by 26,137 · see citing works
The ferritins: molecular properties, iron storage function and cellular regulation
Harrison, P. M., & Arosio, P. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00022-9 · Cited by 2,667 · see citing works
Heme oxygenase 1 is required for mammalian iron reutilization
Poss, K. D., & Tonegawa, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10919 · Cited by 1,016 · see citing works
Why are proteins O-glycosylated?
Jentoft, N. (1990) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(90)90014-3 · Cited by 705 · see citing works
Lanford, R. E., Kanda, P., & Kennedy, R. C. (1986) · Cell · doi:10.1016/0092-8674(86)90883-4 · Cited by 396 · see citing works
O-Glycosylation of Nuclear and Cytosolic Proteins
Comer, F. I., & Hart, G. W. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.r000010200 · Cited by 361 · see citing works
Characterization of a Mouse Monoclonal Antibody Specific for O-Linked N-Acetylglucosamine
Comer, F. I., Vosseller, K., Wells, L., Accavitti, M. A., & Hart, G. W. (2001) · Analytical Biochemistry · doi:10.1006/abio.2001.5132 · Cited by 295 · see citing works
Dynamic O-Glycosylation of Nuclear and Cytosolic Proteins
Wells, L., Gao, Y., Mahoney, J. A., Vosseller, K., Chen, C., Rosen, A., & Hart, G. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109656200 · Cited by 246 · see citing works
Ferritin, transferrin, and iron in selected regions of the adult and aged rat brain
Benkovic, S. A., & Connor, J. R. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903380108 · Cited by 238 · see citing works
Self-citationWells, L., & Hart, G. W. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00641-0 · Cited by 205 · see citing works
Oxidative Damage to DNA Constituents by Iron-mediated Fenton Reactions
Henle, E. S., Luo, Y., Gassmann, W., & Linn, S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21177 · Cited by 175 · see citing works
Characterization of a novel brain‐derived microglial cell line isolated from neonatal rat brain
Cheepsunthorn, P., Radov, L. A., Menzies, S. L., Reid, J., & Connor, J. R. (2001) · Glia · doi:10.1002/glia.1070 · Cited by 163 · see citing works
Self-citationOxidative Damage to DNA Constituents by Iron-mediated Fenton Reactions
Luo, Y., Henle, E. S., & Linn, S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21167 · Cited by 159 · see citing works
Iron and transferrrin uptake by brain and cerebrospinal fluid in the rat
Crowe, A. P., & Morgan, E. H. (1992) · Brain Research · doi:10.1016/0006-8993(92)91652-u · Cited by 150 · see citing works
Alloxan is an inhibitor of the enzyme O-linked N-acetylglucosamine transferase
Konrad, R. J., Zhang, F., Hale, J. E., Knierman, M. D., Becker, G. W., & Kudlow, J. E. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00200-0 · Cited by 146 · see citing works
Nucleocytoplasmic exchange of macromolecules
Paine, P. L., & Feldherr, C. M. (1972) · Experimental Cell Research · doi:10.1016/0014-4827(72)90483-1 · Cited by 145 · see citing works
On the Carcinogenicity of an Iron-Dextran Complex 2
Haddow, A., & Horning, E. S. (1960) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/24.1.109 · Cited by 135 · see citing works
Cozzi, A., Corsi, B., Levi, S., Santambrogio, P., Biasiotto, G., & Arosio, P. (2004) · Blood · doi:10.1182/blood-2003-06-1842 · Cited by 132 · see citing works
Self-citationNuclear Ferritin Protects DNA From UV Damage in Corneal Epithelial Cells
Cai, C. X., Birk, D. E., & Linsenmayer, T. F. (1998) · Molecular Biology of the Cell · doi:10.1091/mbc.9.5.1037 · Cited by 122 · see citing works
Levi, S., & Arosio, P. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2003.10.020 · Cited by 120 · see citing works
Regulation, mechanisms and proposed function of ferritin translocation to cell nuclei
Thompson, K. J., Fried, M. G., Ye, Z., Boyer, P., & Connor, J. R. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.10.2165 · Cited by 110 · see citing works
Self-citationImmunochemical characterization of human liver and heart ferritins with monoclonal antibodies
Luzzago, A., Arosio, P., Iacobello, C., Ruggeri, G., Capucci, L., Brocchi, E., Simone, F., Gamba, D., Gabri, E., Levi, S., et al. (1986) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/0167-4838(86)90147-0 · Cited by 93 · see citing works
Nucleocytoplasmic O-glycosylation: O-GlcNAc and functional proteomics
Vosseller, K., Wells, L., & Hart, G. W. (2001) · Biochimie · doi:10.1016/s0300-9084(01)01295-0 · Cited by 89 · see citing works
Turner, J. R., Tartakoff, A. M., & Greenspan, N. S. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.15.5608 · Cited by 75 · see citing works
Interactions and Reactions of Ferritin with DNA
Surguladze, N., Thompson, K., Beard, J. L., Connor, J. R., & Fried, M. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313348200 · Cited by 73 · see citing works
Self-citationKwok, J., & Richardson, D. R. (2004) · Molecular Pharmacology · doi:10.1124/mol.65.1.181 · Cited by 71 · see citing works
Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload
Smith, A. G., Carthew, P., Francis, J. E., Edwards, R., & Dinsdale, D. D. (1990) · Hepatology · doi:10.1002/hep.1840120622 · Cited by 67 · see citing works
Ernst, J. F., & Prill, S. K. ‐. (2001) · Medical Mycology · doi:10.1080/mmy.39.1.67.74 · Cited by 65 · see citing works
Iron-induced DNA damage and synthesis in isolated rat liver nuclei
Shires, T. K. (1982) · Biochemical Journal · doi:10.1042/bj2050321 · Cited by 62 · see citing works
Brain iron: location and function.
Beard, J. L., Connor, J. D., & Jones, B. C. (1993) · PubMed · Cited by 62 · see citing works
Self-citationFerric and Cupric Ions Requirement for DNA Single-Strand Breakage by H2O2
Tachon, P. (1989) · Free Radical Research Communications · doi:10.3109/10715768909088155 · Cited by 61 · see citing works
Ferritin Is a Developmentally Regulated Nuclear Protein of Avian Corneal Epithelial Cells
Cai, C. X., Birk, D. E., & Linsenmayer, T. F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.19.12831 · Cited by 55 · see citing works
Interaction of lipid peroxidation products with nuclear macromolecules
Vaca, C. E., & Harms‐Ringdahl, M. (1989) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(89)90304-4 · Cited by 44 · see citing works
The Identification of Subcellular Fractions from Mammalian Cells
Graham, J. M. (2003) · Humana Press eBooks · doi:10.1385/0-89603-236-1:1 · Cited by 43 · see citing works
Nuclear translocation of ferritin in corneal epithelial cells
Cai, C. X., & Linsenmayer, T. F. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.12.2327 · Cited by 41 · see citing works
Iron overload of the liver in the baboon
Iancu, T. C., Rabinowitz, H., Brissot, P., Guillouzo, A., Deugnier, Y., & Bourel, M. (1985) · Journal of Hepatology · doi:10.1016/s0168-8278(85)80054-4 · Cited by 39 · see citing works
THE INTRACELLULAR DISTRIBUTION OF FERRITIN FOLLOWING MICROINJECTION
Feldherr, C. M. (1962) · The Journal of Cell Biology · doi:10.1083/jcb.12.1.159 · Cited by 36 · see citing works
Cavanna, F., Ruggeri, G., Iacobello, C., Chieregatti, G., Murador, E., Albertini, A., & Arosio, P. (1983) · Clinica Chimica Acta · doi:10.1016/0009-8981(83)90373-x · Cited by 32 · see citing works
Ferritoid, a Tissue-specific Nuclear Transport Protein for Ferritin in Corneal Epithelial Cells
Millholland, J. M., Fitch, J. M., Cai, C. X., Gibney, E. P., Beazley, K. E., & Linsenmayer, T. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210050200 · Cited by 30 · see citing works
The Expression of Ferritin Subunits and Iron in Oligodendrocytes in Neonatal Porcine Brains
Blissman, G., Menzies, S. B. S., Beard, J. L., Palmer, C., & Connor, J. R. (2007) · Developmental Neuroscience · doi:10.1159/000111417 · Cited by 28 · see citing works
Self-citationCARCINOGENICITY OF IRON-DEXTRAN COMPLEX
Duthie, J. J. R., GIRDWOOD, R. H., Hubble, D., et al. (1960) · The Lancet · doi:10.1016/s0140-6736(60)91298-8 · Cited by 27 · see citing works
Pountney, D., Trugnan, G., Bourgeois, M., & Beaumont, C. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.6.825 · Cited by 27 · see citing works
Ernst, J. F., & Prill, S. K. ‐. (2001) · PubMed · Cited by 25 · see citing works
Microinjection studies of protein transit across the nuclear envelope of human cells*1
Stacey, D. W. (1984) · Experimental Cell Research · doi:10.1016/0014-4827(84)90687-6 · Cited by 24 · see citing works
Cazzola, M., Arosio, P., Bellotti, V., et al. (1985) · British Journal of Haematology · doi:10.1111/j.1365-2141.1985.tb02848.x · Cited by 23 · see citing works
Hurta, R. A. R., & Wright, J. A. (1991) · Biochemistry and Cell Biology · doi:10.1139/o91-094 · Cited by 15 · see citing works
Development of a fluorescent reporter to assess iron regulatory protein activity in living cells
Henderson, R. J., Patton, S. M., & Connor, J. R. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2004.09.032 · Cited by 13 · see citing works
Self-citationHaamedi, S. N., Karten, H. J., & Djamgoz, M. B. A. (2001) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20010319)431:4 · Cited by 8 · see citing works
Sakurai, K., & Miura, T. (1988) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.36.4534 · Cited by 7 · see citing works
Iron release from ferritin by alloxan radical
Miura, T., & Sakurai, K. (1988) · Life Sciences · doi:10.1016/0024-3205(88)90365-7 · Cited by 3 · see citing works
Evaluation of heart isoferritins in serum using specific monoclonal antibodies
Cavanna, F., Ruggeri, G., Chieregatti, G., et al. (1984) · La Ricerca in Clinica e in Laboratorio · doi:10.1007/bf02904856 · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [13]Cheepsunthorn P., Palmer C., Connor J. R. Cellular distribution of ferritin subunits in postnatal rat brain. J. Comp. Neurol. 1998;400:73–86. [PubMed] [Google Scholar]
- [23]Broyles R. H., Blair F. C., Kyker K. D., Kurein B. T., Stewart D. R., Hala'sz H., Berg P. E., Schechter A. N. A ferritin-like protein binds to a highly conserved CAGTGC sequence in the beta-globin promoter. In: Beuzard Y., Lubin B., Rosa J., editors. Sickle Cell Disease and Thalassamias: New Trends in Therapy. Paris: Colloque INSERM/John Libbey Eurotext Ltd; 1995. pp. 43–51. [Google Scholar]
- [34]Bittman K. Glen Mills, PA: 2004. Mean Pixel Density Analysis of ImagePro Software for Fluorescent Quantitation. Phase 3 Imaging. [Google Scholar]
Cited by
Sorted by citations
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 · see citing works
Kell, D. B., & Pretorius, E. (2014) · Metallomics · doi:10.1039/c3mt00347g · Cited by 667 · see citing works
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 · see citing works
Chemistry and biology of ferritin
Plays, M., Müller, S., & Rodriguez, R. (2021) · Metallomics · doi:10.1093/mtomcs/mfab021 · Cited by 232 · see citing works
Storr, H. L., Kind, B., Parfitt, D. A., Chapple, J. P., Lorenz, M., Koehler, K., Huebner, A., & Clark, A. J. L. (2009) · Molecular Endocrinology · doi:10.1210/me.2009-0056 · Cited by 84 · see citing works
- Authors
- SURGULADZE, N., PATTON, S., COZZI, A., FRIED, M. G., & CONNOR, J. R.
- Affiliations
- Pennsylvania State University (US)
- Biological and Technological Research Department, Istituto di Ricovero e Cura a Carattere Scientifico, H. San Raffaele, Via Olgettina 58, 20132 Milan, Italy
- University of Kentucky (US)
- Corresponding author
- SURGULADZE, Nodar
- PATTON, Stephanie
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2005-06-07
- Volume
- 388
- Issue
- 3
- Pages
- 731-740
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1183451
- OpenAlex
- W2087670043
- Cited by
- 81
- References
- 53
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 1 · 2012: 2
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM070662)
- 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
- H-ferritin, O-glycosylation, heterochromatin, iron storage, astrocytoma cells, alloxan, iron depletion, post-translational regulation
- MeSH terms
- Alloxan, Apoferritins, Cell Nucleus, Cytoplasm, Deoxyribonucleases, Ferritins, Glycosylation, Humans, Iron, RNA, Messenger, Protein Biosynthesis, Protein Subunits, Active Transport, Cell Nucleus, RNA Interference, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
