Human L-ferritin deficiency is characterized by idiopathic generalized seizures and atypical restless leg syndrome
Open accessAbstract
The ubiquitously expressed iron storage protein ferritin plays a central role in maintaining cellular iron homeostasis. Cytosolic ferritins are composed of heavy (H) and light (L) subunits that co-assemble into a hollow spherical shell with an internal cavity where iron is stored. The ferroxidase activity of the ferritin H chain is critical to store iron in its Fe3+ oxidation state, while the L chain shows iron nucleation properties. We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). We show that L chain ferritin is undetectable in primary fibroblasts from the patient, and thus ferritin consists only of H chains. Increased iron incorporation into the FtH homopolymer leads to reduced cellular iron availability, diminished levels of cytosolic catalase, SOD1 protein levels, enhanced ROS production and higher levels of oxidized proteins. Importantly, key phenotypic features observed in fibroblasts are also mirrored in reprogrammed neurons from the patient’s fibroblasts. Our results demonstrate for the first time the pathophysiological consequences of L-ferritin deficiency in a human and help to define the concept for a new disease entity hallmarked by idiopathic generalized seizure and atypical RLS.
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?
Neuroferritinopathy is a rare NBIA condition caused by a mutation in the coding region of the FTL gene.
“A paradigmatic yet rare NBIA condition is the neuroferritinopathy that is caused by a mutation in the coding region of the FTL gene [44, 45].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [44]
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
Two to tango: Regulation of Mammalian iron metabolism
Hentze, M. W., Muckenthaler, M. U., Galy, B., & Camaschella, C. (2010) · Cell · doi:10.1016/j.cell.2010.06.028 · Cited by 2,120 · see citing works
Self-citationGlutathione, oxidative stress and neurodegeneration
Schulz, J. B., Lindenau, J. H., Seyfried, J., & DICHGANS, J. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01595.x · Cited by 1,215 · see citing works
Direct generation of functional dopaminergic neurons from mouse and human fibroblasts
Caiazzo, M., Dell’Anno, M. T., Dvoretskova, E., Lazarević, D., Taverna, S., Leo, D., Sotnikova, T. D., Menegon, A., Roncaglia, P., Colciago, G., et al. (2011) · Nature · doi:10.1038/nature10284 · Cited by 1,009 · see citing works
Self-citationSolving the structure of human H ferritin by genetically engineering intermolecular crystal contacts
Lawson, D. M., Artymiuk, P. J., Yewdall, S. J., Smith, J. M. A., Livingstone, J. C., Treffry, A., Luzzago, A., Levi, S., Arosio, P., Cesareni, G., et al. (1991) · Nature · doi:10.1038/349541a0 · Cited by 777 · see citing works
Self-citationPigeolet, E., Corbisier, P., Houbion, A., Lambert, D., Michiels, C., Raes, M. J., Zachary, M.-D., & Remacle, J. (1990) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(90)90078-t · Cited by 740 · see citing works
Iron Deficiency and Brain Development
Lozoff, B., & Georgieff, M. (2006) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2006.08.004 · Cited by 711 · see citing works
Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA functionPreprint
Isken, O., & Maquat, L. E. (2007) · Genes & Development · doi:10.1101/gad.1566807 · Cited by 584 · see citing works
The serine protease TMPRSS6 is required to sense iron deficiency
Du, X., She, E., Gelbart, T., Truksa, J., Lee, P., Xia, Y., Khovananth, K., Mudd, S., Mann, N., Moresco, E. M. Y., et al. (2008) · Science · doi:10.1126/science.1157121 · Cited by 578 · see citing works
MRI measurement of brain iron in patients with restless legs syndrome
Allen, R. P., Barker, P. B., Wehrl, F., Song, H. K., & Earley, C. J. (2001) · Neurology · doi:10.1212/wnl.56.2.263 · Cited by 570 · see citing works
Ferritin: design and formation of an iron-storage molecule
Ford, G. C., Harrison, P. M., Rice, D. W., Smith, J. M., Treffry, A., WHITE, J. L., & Yariv, J. (1984) · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · doi:10.1098/rstb.1984.0046 · Cited by 567 · see citing works
Curtis, A. R. J., Fey, C., Morris, C. M., Bindoff, L. A., Ince, P. G., Chinnery, P. F., Coulthard, A., Jackson, M. J., Jackson, A. P., McHale, D. P., et al. (2001) · Nature Genetics · doi:10.1038/ng571 · Cited by 537 · see citing works
A human mitochondrial ferritin encoded by an intronless gene
Levi, S., Corsi, B., Bosisio, M., Invernizzi, R., Volz, A., Sanford, D., Arosio, P., & Drysdale, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100141200 · Cited by 400 · see citing works
Self-citationDopamine and iron in the pathophysiology of restless legs syndrome (RLS)
Allen, R. P. (2004) · Sleep Medicine · doi:10.1016/j.sleep.2004.01.012 · Cited by 380 · see citing works
Levi, S., Luzzago, A., Cesareni, G., Cozzi, A., Franceschinelli, F., Albertini, A., & Arosio, P. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)81326-1 · Cited by 378 · see citing works
Self-citationIron Toxicity in Diseases of Aging: Alzheimer's Disease, Parkinson's Disease and Atherosclerosis
Altamura, S., & Muckenthaler, M. U. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-1010 · Cited by 369 · see citing works
Self-citationArosio, P., & Levi, S. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2010.02.005 · Cited by 320 · see citing works
Self-citationThe diagnosis and treatment of iron deficiency and its potential relationship to hair loss
Trost, L. B., Bergfeld, W. F., & Calogeras, E. (2006) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2005.11.1104 · Cited by 296 · see citing works
Beaumont, C., Leneuve, P., Devaux, I., Scoazec, J.-Y., Berthier, M., Loiseau, M.-N., Grandchamp, B., & Bonneau, D. (1995) · Nature Genetics · doi:10.1038/ng1295-444 · Cited by 293 · see citing works
The role of iron in restless legs syndrome
Allen, R. P., & Earley, C. J. (2007) · Movement Disorders · doi:10.1002/mds.21607 · Cited by 280 · see citing works
Rouault, T. A., & Cooperman, S. (2006) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2006.08.002 · Cited by 280 · see citing works
Early Embryonic Lethality of H Ferritin Gene Deletion in Mice
Ferreira, C., Bucchini, D., Martin, M.-E., Levi, S., Arosio, P., Grandchamp, B., & Beaumont, C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.5.3021 · Cited by 275 · see citing works
Self-citationEvidence of H- and L-chains have co-operative roles in the iron-uptake mechanism of human ferritin
Levi, S., Yewdall, S. J., Harrison, P. M., Santambrogio, P., Cozzi, A., Rovida, E., Albertini, A., & Arosio, P. (1992) · Biochemical Journal · doi:10.1042/bj2880591 · Cited by 268 · see citing works
Self-citationDirect lineage conversions: unnatural but useful?
Vierbuchen, T., & Wernig, M. (2011) · Nature Biotechnology · doi:10.1038/nbt.1946 · Cited by 259 · see citing works
MRI-determined regional brain iron concentrations in early- and late-onset restless legs syndrome
Earley, C. J., Barker, P. B., Horská, A., & Allen, R. P. (2006) · Sleep Medicine · doi:10.1016/j.sleep.2005.11.009 · Cited by 250 · see citing works
Profile of altered brain iron acquisition in restless legs syndrome
Connor, J. R., Ponnuru, P., Wang, X.-S., Patton, S. M., Allen, R. P., & Earley, C. J. (2011) · Brain · doi:10.1093/brain/awr012 · Cited by 244 · see citing works
Overexpression of Wild Type and Mutated Human Ferritin H-chain in HeLa Cells
Cozzi, A., Corsi, B., Levi, S., Santambrogio, P., Albertini, A., & Arosio, P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003797200 · Cited by 242 · see citing works
Self-citationRole of Iron in Neurodegenerative Disorders
Berg, D., & Youdim, M. B. H. (2006) · Topics in Magnetic Resonance Imaging · doi:10.1097/01.rmr.0000245461.90406.ad · Cited by 227 · see citing works
The Role of the L-Chain in Ferritin Iron Incorporation
Levi, S., Santambrogio, P., Cozzi, A., Rovida, E., Corsi, B., Tamborini, E., Spada, S., Albertini, A., & Arosio, P. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1325 · Cited by 180 · see citing works
Self-citationSpecific iron chelators determine the route of ferritin degradation
De Domenico, I., Ward, D. M., & Kaplan, J. (2009) · Blood · doi:10.1182/blood-2009-05-224188 · Cited by 176 · see citing works
Thompson, K., Menzies, S. L., Muckenthaler, M. U., Torti, F. M., Wood, T. L., Torti, S. V., Hentze, M. W., Beard, J., & Connor, J. R. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10463 · Cited by 168 · see citing works
Self-citationCampanella, A., Rovelli, E., Santambrogio, P., Cozzi, A., Taroni, F., & Levi, S. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn308 · Cited by 162 · see citing works
Self-citationProduction and characterization of recombinant heteropolymers of human ferritin H and L chains
Santambrogio, P., Levi, S., Cozzi, A., Rovida, E., Albertini, A., & Arosio, P. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31451-0 · Cited by 161 · see citing works
Self-citationVidal, R., Ghetti, B. F., Takao, M., Brefel‐Courbon, C., Uro‐Coste, E., Glazier, B. S., Siani, V., Benson, M. D., Calvas, P., Miravalle, L., et al. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.4.363 · Cited by 161 · see citing works
Multiple Pathways for Mineral Core Formation in Mammalian Apoferritin. The Role of Hydrogen Peroxide
Zhao, G., Bou‐Abdallah, F., Arosio, P., Levi, S., Janus-Chandler, C., & Chasteen, N. D. (2003) · Biochemistry · doi:10.1021/bi027357v · Cited by 155 · see citing works
Self-citationMultiregional brain iron deficiency in restless legs syndrome
Godau, J., Klose, U., Santo, A. D., Schweitzer, K. J., & Berg, D. (2008) · Movement Disorders · doi:10.1002/mds.22070 · Cited by 144 · see citing works
Santambrogio, P., Levi, S., Arosio, P., Palagi, L., Vecchio, G., Lawson, D. M., Yewdall, S. J., Artymiuk, P. J., Harrison, P. M., & Jappelli, R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49681-6 · Cited by 143 · see citing works
Self-citationEffect of Iron Supplementation on Oxidative Stress and Antioxidant Status in Iron-Deficiency Anemia
Kurtoğlu, E., Uğur, A., Baltacı, A. K., & Ündar, L. (2003) · Biological Trace Element Research · doi:10.1385/bter:96:1-3:117 · Cited by 143 · see citing works
Iron, the substantia nigra and related neurological disorders
Snyder, A. M., & Connor, J. R. (2008) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.08.005 · Cited by 137 · see citing works
Earley, C. J., Horská, A., Mohamed, M. A., Barker, P. B., Beard, J. L., & Allen, R. P. (2008) · Sleep Medicine · doi:10.1016/j.sleep.2007.12.006 · 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 · cited 3× · see citing works
“, 2000) and RNA interference studies in HeLa cells (Cozzi et al., 2004), indicated that alterations of FtL levels do not affect cellular iron homeostasis or the sensitivity to oxidative stress.”
BackgroundSelf-citationRole of Ferritin in the Control of the Labile Iron Pool in Murine Erythroleukemia Cells
Picard, V., Epsztejn, S., Santambrogio, P., Cabantchik, Z. I., & Beaumont, C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.25.15382 · Cited by 131 · see citing works
Self-citationMissirlis, F., Kosmidis, S., Brody, T., Mavrakis, M., Holmberg, S. K. S., Odenwald, W. F., Skoulakis, E. M. C., & Rouault, T. A. (2007) · Genetics · doi:10.1534/genetics.107.075150 · Cited by 131 · see citing works
Iron Regulatory Proteins: From Molecular Mechanisms to Drug Development
Recalcati, S., Minotti, G., & Cairo, G. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2983 · Cited by 123 · 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
Self-citationLanglois d'Estaintot, B., Santambrogio, P., Granier, T., Gallois, B., Chevalier, J. M., Précigoux, G., Levi, S., & Arosio, P. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.04.036 · Cited by 113 · see citing works
Self-citationMutational analysis of the channel and loop sequences of human ferritin H-chain
Levi, S., Luzzago, A., Franceschinelli, F., Santambrogio, P., Cesareni, G., & Arosio, P. (1989) · Biochemical Journal · doi:10.1042/bj2640381 · Cited by 104 · see citing works
Self-citationNeurodegeneration With Brain Iron Accumulation: From Genes to Pathogenesis
Hayflick, S. J. (2006) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2006.08.007 · Cited by 102 · see citing works
Sun, S., Arosio, P., Levi, S., & Chasteen, N. D. (1993) · Biochemistry · doi:10.1021/bi00087a015 · Cited by 99 · see citing works
Self-citationRomão, L., Inácio, Â., Santos, S., Ávila, M. J. D. M., Faustino, P., Pacheco, P. R., & Lavinha, J. (2000) · Blood · doi:10.1182/blood.v96.8.2895 · Cited by 92 · see citing works
H ferritin knockout mice: a model of hyperferritinemia in the absence of iron overload
Ferreira, C., Santambrogio, P., Martin, M.-E., Andrieu, V., Feldmann, G., Hénin, D., & Beaumont, C. (2001) · Blood · doi:10.1182/blood.v98.3.525 · Cited by 90 · see citing works
Self-citationUpdate in restless legs syndrome
Salas, R. M. E., Gamaldo, C. E., & Allen, R. P. (2010) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32833bcdd8 · Cited by 86 · see citing works
Conditional deletion of ferritin H in mice induces loss of iron storage and liver damage #
Darshan, D., Vanoaica, L., Richman, L., Beermann, F., & Kühn, L. C. (2009) · Hepatology · doi:10.1002/hep.23058 · Cited by 86 · see citing works
Kannengiesser, C., Jouanolle, A., Hetet, G., Mosser, A., Muzeau, F., Henry, D., Bardou‐Jacquet, E., Mornet, M., Brissot, P., Deugnier, Y., et al. (2009) · Haematologica · doi:10.3324/haematol.2008.000125 · Cited by 85 · see citing works
Neuroferritinopathy: a neurodegenerative disorder associated with L-ferritin mutation
Levi, S., Cozzi, A., & Arosio, P. (2005) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2004.08.021 · Cited by 84 · see citing works
Self-citationOxidation-induced ferritin turnover in microglial cells: role of proteasome
Mehlhase, J., Sandig, G., Pantopoulos, K., & Grune, T. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.10.025 · Cited by 84 · see citing works
Acute and chronic effects of developmental iron deficiency on mRNA expression patterns in the brain
Clardy, S. L., Wang, X., Zhao, W., Liu, W., Chase, G. A., Beard, J. L., Felt, B. T., & Connor, J. R. (2006) · Springer eBooks · doi:10.1007/978-3-211-33328-0_19 · Cited by 82 · see citing works
Oxidative stress and cell death in cells expressing L-ferritin variants causing neuroferritinopathy
Cozzi, A., Rovelli, E., Frizzale, G., Campanella, A., Amendola, M., Arosio, P., & Levi, S. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.09.009 · Cited by 78 · see citing works
Self-citationFerritin crystal cataracts in hereditary hyperferritinemia cataract syndrome.
Brooks, D. G., Manova-Todorova, K. O., Farmer, J., Lobmayr, L., Wilson, R. B., Eagle, R. C., Pierre, T. G. S., & Stambolian, D. (2002) · PubMed · Cited by 72 · see citing works
Mitochondrial Ferritin in the Substantia Nigra in Restless Legs Syndrome
Snyder, A. M., Wang, X., Patton, S. M., Arosio, P., Levi, S., Earley, C. J., Allen, R. P., & Connor, J. R. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181bdc44f · Cited by 71 · see citing works
Self-citationIron Insufficiency Compromises Motor Neurons and Their Mitochondrial Function in Irp2-Null Mice
Jeong, S. Y., Crooks, D. R., Ollivierre, H., Ghosh, M. C., Sougrat, R., Lee, J., Cooperman, S. S., Mitchell, J. B., Beaumont, C., & Rouault, T. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025404 · Cited by 62 · see citing works
Lower molecular weight intravenous iron dextran for restless legs syndrome
Cho, Y. W., Allen, R. P., & Earley, C. J. (2013) · Sleep Medicine · doi:10.1016/j.sleep.2012.11.001 · Cited by 62 · see citing works
Pathophysiology of restless legs syndrome: Evidence for iron involvement
Connor, J. R. (2008) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-008-0026-x · Cited by 55 · see citing works
Luscieti, S., Santambrogio, P., Langlois d'Estaintot, B., Granier, T., Cozzi, A., Poli, M., Gallois, B., Finazzi, D., Cattaneo, A., Levi, S., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.096404 · Cited by 51 · see citing works
Self-citationIron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis
Idro, R., Gwer, S., Williams, T. N., Otieno, T., Uyoga, S. M., Fegan, G., Kager, P. A., Maitland, K., Kirkham, F. J., Neville, B. G. R., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014001 · Cited by 49 · see citing works
Millonig, G., Muckenthaler, M. U., & Mueller, S. (2010) · Human Genomics · doi:10.1186/1479-7364-4-4-250 · Cited by 46 · see citing works
Self-citationBurn, J., & Chinnery, P. F. (2006) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2006.08.006 · Cited by 44 · see citing works
Iron deficiency anaemia--a risk factor for febrile seizures in children.
Sherjil, A., Saeed, Z. U., Shehzad, S., & Amjad, R. (2010) · PubMed · Cited by 42 · see citing works
Cremonesi, L., Cozzi, A., Girelli, D., Ferrari, F., Fermo, I., Foglieni, B., Levi, S., Bozzini, C., Camparini, M., Ferrari, M., et al. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2003.011718 · Cited by 42 · see citing works
Self-citationÖzaydın, E., Arhan, E., Çetinkaya, B., Özdel, S., Değerli̇yurt, A., Güven, A., & Köse, G. (2012) · Seizure · doi:10.1016/j.seizure.2011.12.014 · Cited by 40 · see citing works
Cozzi, A., Santambrogio, P., Corsi, B., Campanella, A., Arosio, P., & Levi, S. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.05.004 · Cited by 38 · see citing works
Self-citationCozzi, A., Levi, S., Bazzigaluppi, E., Ruggeri, G., & Arosio, P. (1989) · Clinica Chimica Acta · doi:10.1016/0009-8981(89)90052-1 · Cited by 34 · see citing works
Self-citationWan, L., Nie, G., Zhang, J., & Zhao, B. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111169 · Cited by 32 · see citing works
Hair loss in long-term or home parenteral nutrition: are micronutrient deficiencies to blame?
Daniells, S., & Hardy, G. (2010) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32833ece02 · Cited by 31 · see citing works
White, C. W., Nguyen, D.-D. H., Suzuki, K., Taniguchi, N., Rusakow, L. S., Avraham, K. B., & Groner, Y. (1993) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(93)90166-r · Cited by 27 · see citing works
Thurlow, V. R., Vadher, B., Bomford, A. B., DeLord, C., Kannengiesser, C., Beaumont, C., & Grandchamp, B. (2012) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1258/acb.2011.011229 · Cited by 20 · see citing works
Bobby, Z., Rajendiran, S., & Hamide, A. (2012) · Saudi Journal of Gastroenterology · doi:10.4103/1319-3767.98430 · Cited by 13 · see citing works
Structural studies on recombinant human ferritins
Yewdall, S. J., Lawson, D. M., Artymiuk, P. J., Treffry, A., Harrison, P. M., Luzzago, A., Cesareni, G., Levi, S., & Arosio, P. (1990) · Biochemical Society Transactions · doi:10.1042/bst0181028 · Cited by 10 · see citing works
Self-citationDietary Iron and Exposure to Lead Influence Susceptibility to Seizures
Barzideh, O. S., Burright, R. G., & Donovick, P. J. (1995) · Psychological Reports · doi:10.2466/pr0.1995.76.3.971 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A Red carpet for iron metabolism
Muckenthaler, M. U., Rivella, S., Hentze, M. W., & Galy, B. (2017) · Cell · doi:10.1016/j.cell.2016.12.034 · Cited by 1,319 · see citing works
Self-citationWeiss, G., Ganz, T., & Goodnough, L. T. (2019) · Blood · doi:10.1182/blood-2018-06-856500 · Cited by 1,219 · see citing works
Iron Metabolism in Ferroptosis
Chen, X., Yu, C., Kang, R., & Tang, D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.590226 · Cited by 980 · see citing works
Ferritin, cellular iron storage and regulation
Arosio, P., Elia, L., & Poli, M. (2017) · IUBMB Life · doi:10.1002/iub.1621 · Cited by 480 · see citing works
Nemeth, E., & Ganz, T. (2014) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2014.04.005 · Cited by 401 · see citing works
Targeting iron metabolism in drug discovery and delivery
Crielaard, B. J., Lammers, T., & Rivella, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.248 · Cited by 352 · 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
Iron imbalance in neurodegeneration
Levi, S., Ripamonti, M., Moro, A. S., & Cozzi, A. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02399-z · Cited by 214 · see citing works
Self-citation“Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels
Nairz, M., Theurl, I., Swirski, F. K., & Weiss, G. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1944-8 · Cited by 178 · see citing works
Regulation of tissue iron homeostasis: the macrophage “ferrostat”
Winn, N. C., Volk, K. M., & Hasty, A. H. (2020) · JCI Insight · doi:10.1172/jci.insight.132964 · Cited by 177 · see citing works
Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration
Finazzi, D., & Arosio, P. (2014) · Archives of Toxicology · doi:10.1007/s00204-014-1329-0 · Cited by 166 · see citing works
The importance of eukaryotic ferritins in iron handling and cytoprotection
Arosio, P., Carmona, F., Gozzelino, R., Maccarinelli, F., & Poli, M. (2015) · Biochemical Journal · doi:10.1042/bj20150787 · Cited by 104 · see citing works
Coenzyme A corrects pathological defects in human neurons of PANK2‐associated neurodegeneration
Orellana, D. I., Santambrogio, P., Rubio, A., Yekhlef, L., Cancellieri, C., Dusi, S., Giannelli, S. G., Venco, P., Mazzara, P. G., Cozzi, A., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606391 · Cited by 93 · see citing works
Self-citationIron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions
Fujimaki, M., Furuya, N., Saiki, S., Amo, T., Imamichi, Y., & Hattori, N. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00010-19 · Cited by 85 · see citing works
Mora, M., Angelini, C. I., Bignami, F., Bodin, A.-M., Crimi, M., di Donato, J. H., Felice, A. E., Jaeger, C., Karcagi, V., Cam, Y. L., et al. (2014) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.272 · Cited by 83 · see citing works
Self-citationDiagnosis of iron-deficient states
Archer, N. M., & Brugnara, C. (2015) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2015.1038744 · Cited by 82 · see citing works
Santambrogio, P., Dusi, S., Guaraldo, M., Rotundo, L. I., Broccoli, V., Garavaglia, B., Tiranti, V., & Levi, S. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.02.030 · Cited by 78 · see citing works
Self-citationTherapeutic Insights on Ferroptosis in Parkinson's disease
Thapa, K., Khan, H., Kanojia, N., Singh, T. G., Kaur, A., & Kaur, G. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175133 · Cited by 78 · see citing works
Systemic and Cerebral Iron Homeostasis in Ferritin Knock-Out Mice
Li, W., Garringer, H. J., Goodwin, C. B., Richine, B. M., Acton, A. J., VanDuyn, N., Muhoberac, B. B., Irimia, J. M., Chan, R. J., Peacock, M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117435 · Cited by 61 · see citing works
Iron Homeostasis in Peripheral Nervous System, Still a Black Box?
Levi, S., & Taveggia, C. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5813 · Cited by 38 · see citing works
Self-citationRegulation of iron homeostasis: Lessons from mouse models
Altamura, S., Marques, O., Colucci, S., Mertens, C., Alikhanyan, K., & Muckenthaler, M. U. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100872 · Cited by 35 · see citing works
Self-citationH ferritin silencing induces protein misfolding in K562 cells: A Raman analysis
Zolea, F., Biamonte, F., Candeloro, P., Sanzo, M. D., Cozzi, A., Vito, A. D., Quaresima, B., Lobello, N., Trecroci, F., Fabrizio, E. M. D., et al. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.07.161 · Cited by 30 · see citing works
Self-citationCadenas, B., Fita‐Torró, J., Cortés, M. B., Hernández‐Rodríguez, I., Fuster, J. L., Llinares, M. E., Galera, A., Romero, J., Pérez-Montero, S., Tornador, C., et al. (2019) · Pharmaceuticals · doi:10.3390/ph12010017 · Cited by 28 · see citing works
Zhang, L., Fang, J. S., Tang, Z., & Luo, Y. (2022) · International Journal of Medical Sciences · doi:10.7150/ijms.76660 · Cited by 24 · see citing works
Pathogenic mechanism and modeling of neuroferritinopathy
Cozzi, A., Santambrogio, P., Ripamonti, M., Rovida, E., & Levi, S. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03747-w · Cited by 18 · see citing works
Self-citationTao, J., Zhou, J., Zhu, H., Xu, L., Yang, J., Mu, X., & Fan, X. L. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1503064 · Cited by 16 · see citing works
Santambrogio, P., Cozzi, A., Meo, I. D., Cavestro, C., Vergara, C., Rodríguez‐Pascau, L., Martinell, M., Pizcueta, P. M., Tiranti, V., & Levi, S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15010202 · Cited by 12 · see citing works
Self-citationJerez, P. Á., Alcantud, J. L., Reyes‐Ramírez, L. D. L., Moore, A. K., Ruz, C., Montero, F. V., Rodríguez-Losada, N., Saini, P., Gan‐Or, Z., Alvarado, C. X., et al. (2023) · npj Parkinson s Disease · doi:10.1038/s41531-023-00496-y · Cited by 12 · see citing works
The SENIORLAB study in the quest for healthy elderly patients
Risch, M., Sakem, B., Risch, L., & Nydegger, U. E. (2018) · Journal of Laboratory Medicine · doi:10.1515/labmed-2018-0034 · Cited by 10 · see citing works
Iron role paradox in nerve degeneration and regeneration
Bolandghamat, S., & Rassouli, M. B. (2024) · Physiological Reports · doi:10.14814/phy2.15908 · Cited by 8 · see citing works
Shagidov, D., Guttmann‐Raviv, N., Cunat, S., Frech, L., Giansily‐Blaizot, M., Ghatpande, N., Abelya, G., Frank, G. A., Aguilar‐Martinez, P., & Meyron‐Holtz, E. G. (2023) · American Journal of Hematology · doi:10.1002/ajh.27124 · Cited by 7 · see citing works
Nydegger, U. E., & Lung, T. (2023) · Springer eBooks · doi:10.1007/978-3-031-32276-1_9 · Cited by 6 · see citing works
Gruberova, E., Pekařík, V., Musílek, K., & Heger, Z. (2025) · Nano Today · doi:10.1016/j.nantod.2025.102648 · Cited by 5 · see citing works
Iron Metabolism and Related Disorders
Ginzburg, Y. Z., & Finberg, K. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-812535-9.00012-1 · Cited by 4 · see citing works
Rathkolb, B., Klempt, M., Sabrautzki, S., Michel, D., Klaften, M., Laufs, J., Sedlmeier, R., Hans, W., Fuchs, H., Muckenthaler, M. U., et al. (2015) · BioMetals · doi:10.1007/s10534-015-9824-1 · Cited by 4 · see citing works
Self-citationEpilepsy Treatment and Nutritional Intervention
Majkowski, J. (2014) · InTech eBooks · doi:10.5772/57484 · Cited by 3 · see citing works
Sung, Y., Yin, J., Lee, K., Tsai, C., Lin, Y., Chen, S., Chung, C., Chien, W., Lee, J., & Chou, C.-H. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.953821 · Cited by 3 · see citing works
N88S seipin-related seipinopathy is a lipidopathy associated with loss of iron homeostasis
Ribeiro, M. O., Oliveira, M., Nogueira, V. I. J. O., Costa, V., & Teixeira, V. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-024-02007-9 · Cited by 1 · see citing works
Alternative Human Cell Models for Neuropsychiatric Research
Lo, B. D., Chang, D. J., & Kano, S. (2015) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-800981-9.00024-9 · Cited by 1 · see citing works
The higher prevalence of non-right handers among patients with restless leg syndrome
Ghourchian, S., & Bahrami, P. (2014) · Neurological Sciences · doi:10.1007/s10072-014-1860-z
A 3′-truncating FTL mutation associated with hypoferritinemia without neuroferritinopathy
Turner, S., Dress, C., & Misra, V. K. (2021) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2021.104159
Mechanism of Ferritin Heavy Chain in the Proliferation and Migration of Prostate Cancer CellsPreprint
Lu, C., Zhao, H., & Zhang, M. (2021) · Research Square · doi:10.21203/rs.3.rs-319708/v1
Mustafa, F., Das, A., Radhakrishnan, D. M., Pandit, A. K., & Srivastava, A. K. (2024) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.13985
Pujol‐Carrion, N., & de la Torre-Ruiz, M. Á. (2025) · Biomolecules · doi:10.3390/biom15030447
Nydegger, U., & Lung, T. (2025) · Springer eBooks · doi:10.1007/978-3-031-94028-6_9
Ferritin light-chain contributes to hair cells function and survival
Petit, C. P., Dodo, S. M. B., Tobón, L. M. J., Harrus, A.-G., Souyris, C., Picot, A., Wang, J., Pujol, R., Venail, F., Vidal, R., et al. (2026) · Communications Biology · doi:10.1038/s42003-026-10069-3
- Authors
- Cozzi, A., Santambrogio, P., Privitera, D., Broccoli, V., Rotundo, L. I., Garavaglia, B., Benz, R., Altamura, S., Goede, J. S., Muckenthaler, M. U., & Levi, S.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Kantonsspital Münsterlingen (CH)
- Heidelberg University (DE)
- University Hospital Zurich (CH)
- Corresponding author
- Levi, Sonia
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2013-08-12
- Volume
- 210
- Issue
- 9
- Pages
- 1779-1791
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC3754865
- OpenAlex
- W2134438683
- Cited by
- 47
- References
- 78
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 7 · 2014: 7
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Dietmar Hopp Stiftung
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Epidemiology › Restless Legs Syndrome Research
- Keywords
- ferritin light chain, iron homeostasis, ferroxidase activity, FTH1, catalase, superoxide dismutase 1, reactive oxygen species, protein oxidation, fibroblasts, loss-of-function mutations, iron storage
- MeSH terms
- Iron Deficiencies, Amino Acid Sequence, Apoferritins, Base Sequence, Child, Female, Fibroblasts, Half-Life, Homozygote, Humans, Iron, Molecular Sequence Data, Neurons, Receptors, Transferrin, Restless Legs Syndrome, Seizures, Reactive Oxygen Species, Oxidative Stress, Codon, Terminator, Membrane Potential, Mitochondrial, Young Adult, Polymerization
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