{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:12:27Z","timestamp":1781730747355,"version":"3.54.5"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T00:00:00Z","timestamp":1539561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"United States - Israel Binational Science Foundation (IL)","award":["2007466"],"award-info":[{"award-number":["2007466"]}]},{"DOI":"10.13039\/100006221","name":"United States - Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["2007466"],"award-info":[{"award-number":["2007466"]}],"id":[{"id":"10.13039\/100006221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1444\/13"],"award-info":[{"award-number":["1444\/13"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0204471","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T17:28:11Z","timestamp":1539624491000},"page":"e0204471","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Orchestrated regulation of iron trafficking proteins in the kidney during iron overload facilitates systemic iron retention"],"prefix":"10.1371","volume":"13","author":[{"given":"Avital","family":"Weiss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior","family":"Spektor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyora","family":"A. Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Lifshitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbar","family":"Magid Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9478-5344","authenticated-orcid":true,"given":"De-Liang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Truman-Rosentsvit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Leichtmann-Bardoogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Nyska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sefi","family":"Addadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey A.","family":"Rouault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-7975","authenticated-orcid":true,"given":"Esther G.","family":"Meyron-Holtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,10,15]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1097\/MPH.0b013e3181fd2aae","article-title":"Human heme oxygenase-1 deficiency presenting with hemolysis, nephritis, and asplenia","volume":"33","author":"N Radhakrishnan","year":"2011","journal-title":"Journal of pediatric hematology\/oncology"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.5527\/wjn.v4.i2.185","article-title":"Pathogenesis of glomerular haematuria","volume":"4","author":"C Yuste","year":"2015","journal-title":"World journal of nephrology"},{"issue":"26","key":"ref3","doi-asserted-by":"crossref","first-page":"6054","DOI":"10.1182\/blood-2010-03-272138","article-title":"Dysfunction of the heme recycling system in heme oxygenase 1-deficient mice: effects on macrophage viability and tissue iron distribution","volume":"116","author":"G Kovtunovych","year":"2010","journal-title":"Blood"},{"issue":"9","key":"ref4","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1182\/blood-2014-02-554162","article-title":"Wild-type macrophages reverse disease in heme oxygenase 1-deficient mice","volume":"124","author":"G Kovtunovych","year":"2014","journal-title":"Blood"},{"issue":"4","key":"ref5","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0950-3536(05)80129-5","article-title":"Clinical spectrum and management of haemochromatosis","volume":"7","author":"C Niederau","year":"1994","journal-title":"Bailliere's clinical haematology"},{"issue":"5","key":"ref6","doi-asserted-by":"crossref","first-page":"814","DOI":"10.3109\/0886022X.2014.892391","article-title":"Renal hemosiderosis and rapidly progressive glomerulonephritis associated with primary hemochromatosis","volume":"36","author":"S Ozkurt","year":"2014","journal-title":"Renal failure"},{"issue":"9602","key":"ref7","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/S0140-6736(07)61782-6","article-title":"Haemochromatosis","volume":"370","author":"PC Adams","year":"2007","journal-title":"Lancet"},{"issue":"3","key":"ref8","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/ki.1993.84","article-title":"Intra-GBM site of the functional filtration barrier for endogenous proteins in rats","volume":"43","author":"Y Fujigaki","year":"1993","journal-title":"Kidney Int"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1046\/j.1523-1755.1999.00234.x","article-title":"Fractional clearance of high molecular weight proteins in conscious rats using a continuous infusion method","volume":"55","author":"MJ Burne","year":"1999","journal-title":"Kidney Int"},{"issue":"2","key":"ref10","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1681\/ASN.2006080908","article-title":"Renal iron metabolism: transferrin iron delivery and the role of iron regulatory proteins","volume":"18","author":"D Zhang","year":"2007","journal-title":"J Am Soc Nephrol"},{"issue":"5","key":"ref11","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1046\/j.1523-1755.2001.00016.x","article-title":"Glomerular protein sieving and implications for renal failure in Fanconi syndrome","volume":"60","author":"AG Norden","year":"2001","journal-title":"Kidney Int"},{"key":"ref12","article-title":"Iron transport in the kidney: implications for physiology and cadmium nephrotoxicity","author":"F Thevenod","year":"2015","journal-title":"Metallomics"},{"issue":"22","key":"ref13","doi-asserted-by":"crossref","first-page":"12491","DOI":"10.1073\/pnas.211291398","article-title":"Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia","volume":"98","author":"R Kozyraki","year":"2001","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"6","key":"ref14","doi-asserted-by":"crossref","first-page":"F1525","DOI":"10.1152\/ajprenal.00359.2005","article-title":"Divalent metal transporter 1 in the kidney proximal tubule is expressed in late endosomes\/lysosomal membranes: implications for renal handling of protein-metal complexes","volume":"290","author":"M Abouhamed","year":"2006","journal-title":"Am J Physiol Renal Physiol"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.kint.2015.11.007","article-title":"Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease","volume":"89","author":"R Nielsen","year":"2016","journal-title":"Kidney Int"},{"issue":"12","key":"ref16","first-page":"759","article-title":"Transferrin receptor expression in normal, iron-deficient and iron-overloaded rats","volume":"39","author":"JP Lu","year":"1989","journal-title":"Acta Pathol Jpn"},{"issue":"5","key":"ref17","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1136\/jcp.36.5.539","article-title":"Transferrin receptors in human tissues: their distribution and possible clinical relevance","volume":"36","author":"KC Gatter","year":"1983","journal-title":"J Clin Pathol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fphar.2014.00124","article-title":"The physiological functions of iron regulatory proteins in iron homeostasis\u2014an update","volume":"5","author":"DL Zhang","year":"2014","journal-title":"Frontiers in pharmacology"},{"issue":"10","key":"ref19","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1172\/JCI119411","article-title":"Identification of rat yolk sac target protein of teratogenic antibodies, gp280, as intrinsic factor-cobalamin receptor","volume":"99","author":"B Seetharam","year":"1997","journal-title":"J Clin Invest"},{"issue":"1","key":"ref20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1084\/jem.167.1.213","article-title":"Characterization of a 280-kD protein restricted to the coated pits of the renal brush border and the epithelial cells of the yolk sac. Teratogenic effect of the specific monoclonal antibodies","volume":"167","author":"D Sahali","year":"1988","journal-title":"The Journal of experimental medicine"},{"issue":"Pt 6","key":"ref21","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1042\/BST0361239","article-title":"The role of Dcytb in iron metabolism: an update","volume":"36","author":"AT McKie","year":"2008","journal-title":"Biochemical Society transactions"},{"issue":"4","key":"ref22","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1182\/blood-2006-02-003681","article-title":"The Steap proteins are metalloreductases","volume":"108","author":"RS Ohgami","year":"2006","journal-title":"Blood"},{"issue":"9","key":"ref23","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1074\/jbc.M114.607507","article-title":"Prion protein promotes kidney iron uptake via its ferrireductase activity","volume":"290","author":"S Haldar","year":"2015","journal-title":"The Journal of biological chemistry"},{"issue":"5","key":"ref24","doi-asserted-by":"crossref","first-page":"F803","DOI":"10.1152\/ajprenal.2001.280.5.F803","article-title":"Cellular localization of divalent metal transporter DMT-1 in rat kidney","volume":"280","author":"CJ Ferguson","year":"2001","journal-title":"Am J Physiol Renal Physiol"},{"issue":"7","key":"ref25","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.bbagen.2008.10.010","article-title":"Iron transport and the kidney","volume":"1790","author":"CP Smith","year":"2009","journal-title":"Biochimica et biophysica acta"},{"issue":"2","key":"ref26","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/84859","article-title":"Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice","volume":"27","author":"T LaVaute","year":"2001","journal-title":"Nature genetics"},{"issue":"2","key":"ref27","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1582-4934.2009.00985.x","article-title":"Ferroportin 1 is expressed basolaterally in rat kidney proximal tubule cells and iron excess increases its membrane trafficking","volume":"15","author":"NA Wolff","year":"2011","journal-title":"J Cell Mol Med"},{"issue":"8","key":"ref28","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1182\/blood-2017-05-786590","article-title":"Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin","volume":"131","author":"S Aschemeyer","year":"2018","journal-title":"Blood"},{"issue":"6383","key":"ref29","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1126\/science.aal2022","article-title":"Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk","volume":"359","author":"DL Zhang","year":"2018","journal-title":"Science (New York, NY"},{"issue":"5704","key":"ref30","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1126\/science.1104742","article-title":"Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization","volume":"306","author":"E Nemeth","year":"2004","journal-title":"Science (New York, NY"},{"issue":"2","key":"ref31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.semnephrol.2016.02.001","article-title":"Iron Balance and the Role of Hepcidin in Chronic Kidney Disease","volume":"36","author":"T Ganz","year":"2016","journal-title":"Seminars in nephrology"},{"issue":"9","key":"ref32","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1182\/blood-2009-11-253815","article-title":"Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway","volume":"116","author":"LA Cohen","year":"2010","journal-title":"Blood"},{"issue":"1","key":"ref33","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1042\/BJ20121139","article-title":"Ferroportin expression in haem oxygenase 1-deficient mice","volume":"449","author":"RR Starzynski","year":"2013","journal-title":"The Biochemical journal"},{"key":"ref34","first-page":"194","article-title":"Ferritin polarization and iron transport across monolayer epithelial barriers in mammals","volume":"5","author":"EG Meyron-Holtz","year":"2014","journal-title":"Frontiers in pharmacology"},{"issue":"1","key":"ref35","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1073\/pnas.1312833110","article-title":"Initial stages of calcium uptake and mineral deposition in sea urchin embryos","volume":"111","author":"N Vidavsky","year":"2014","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.1038\/srep05987","article-title":"Introduction of correlative light and airSEM microscopy imaging for tissue research under ambient conditions","volume":"4","author":"I Solomonov","year":"2014","journal-title":"Scientific reports"},{"issue":"4","key":"ref37","first-page":"223","article-title":"Endocytic receptors in the renal proximal tubule","volume":"27","author":"EI Christensen","year":"2012","journal-title":"Physiology (Bethesda)"},{"issue":"2","key":"ref38","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/sj.emboj.7600041","article-title":"Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis","volume":"23","author":"EG Meyron-Holtz","year":"2004","journal-title":"The EMBO journal"},{"issue":"3","key":"ref39","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1182\/blood-2004-12-4703","article-title":"Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2","volume":"106","author":"SS Cooperman","year":"2005","journal-title":"Blood"},{"issue":"10","key":"ref40","doi-asserted-by":"crossref","first-page":"e25404","DOI":"10.1371\/journal.pone.0025404","article-title":"Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice","volume":"6","author":"SY Jeong","year":"2011","journal-title":"PLoS One"},{"issue":"8","key":"ref41","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nchembio807","article-title":"The role of iron regulatory proteins in mammalian iron homeostasis and disease","volume":"2","author":"TA Rouault","year":"2006","journal-title":"Nature chemical biology"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.nutr.28.061807.155521","article-title":"Systemic iron homeostasis and the iron-responsive element\/iron-regulatory protein (IRE\/IRP) regulatory network","volume":"28","author":"MU Muckenthaler","year":"2008","journal-title":"Annual review of nutrition"},{"issue":"6","key":"ref43","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.freeradbiomed.2010.12.023","article-title":"Regulation of iron pathways in response to hypoxia","volume":"50","author":"NL Chepelev","year":"2011","journal-title":"Free radical biology & medicine"},{"issue":"7","key":"ref44","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nrneph.2015.82","article-title":"Anaemia in kidney disease: harnessing hypoxia responses for therapy","volume":"11","author":"MJ Koury","year":"2015","journal-title":"Nature reviews Nephrology"},{"issue":"3","key":"ref45","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.celrep.2015.12.065","article-title":"NCOA4 Deficiency Impairs Systemic Iron Homeostasis","volume":"14","author":"R Bellelli","year":"2016","journal-title":"Cell reports"},{"key":"ref46","first-page":"C41","article-title":"Iron-induced switching of a receptor mediated transferrin uptake in epithelial cells","volume":"27","author":"M Haley","year":"2012","journal-title":"Proc Physiol Soc"},{"issue":"2","key":"ref47","doi-asserted-by":"crossref","first-page":"260","DOI":"10.3324\/haematol.2016.151621","article-title":"Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Gunther disease model","volume":"102","author":"S Millot","year":"2017","journal-title":"Haematologica"},{"issue":"6","key":"ref48","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s00467-014-3037-7","article-title":"In-depth phenotyping of a Donnai-Barrow patient helps clarify proximal tubule dysfunction","volume":"30","author":"A Dachy","year":"2015","journal-title":"Pediatric nephrology (Berlin, Germany)"},{"issue":"12","key":"ref49","doi-asserted-by":"crossref","first-page":"E1519","DOI":"10.1152\/ajpendo.00007.2012","article-title":"Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload","volume":"302","author":"Y Leichtmann-Bardoogo","year":"2012","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"3","key":"ref50","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1182\/blood-2017-02-768580","article-title":"Ferritin is secreted via 2 distinct nonclassical vesicular pathways","volume":"131","author":"M Truman-Rosentsvit","year":"2018","journal-title":"Blood"},{"issue":"12","key":"ref51","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1016\/j.bbamcr.2016.09.008","article-title":"Erythroid cell mitochondria receive endosomal iron by a &quot;kiss-and-run&quot; mechanism","volume":"1863","author":"A Hamdi","year":"2016","journal-title":"Biochimica et biophysica acta"},{"key":"ref52","article-title":"Endosome-mitochondria interactions are modulated by iron release from transferrin","author":"A Das","year":"2016","journal-title":"J Cell Biol"},{"issue":"7","key":"ref53","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1182\/blood-2005-04-1365","article-title":"Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2)","volume":"106","author":"B Galy","year":"2005","journal-title":"Blood"},{"issue":"9","key":"ref54","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.bbamcr.2012.03.004","article-title":"Ferroportin-mediated iron transport: expression and regulation","volume":"1823","author":"DM Ward","year":"2012","journal-title":"Biochimica et biophysica acta"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1186\/1471-2164-8-379","article-title":"Effects of iron loading on muscle: genome-wide mRNA expression profiling in the mouse","volume":"8","author":"A Rodriguez","year":"2007","journal-title":"BMC genomics"},{"issue":"4","key":"ref56","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/ki.2013.142","article-title":"Hepcidin regulates intrarenal iron handling at the distal nephron","volume":"84","author":"B Moulouel","year":"2013","journal-title":"Kidney Int"},{"issue":"51","key":"ref57","first-page":"1","article-title":"Some physicochemical aspects of iron metabolism","author":"P. Aisen","year":"1976","journal-title":"Ciba Found Symp"},{"issue":"10","key":"ref58","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1056\/NEJM199503093321006","article-title":"Hypoxia of the renal medulla\u2014its implications for disease","volume":"332","author":"M Brezis","year":"1995","journal-title":"N Engl J Med"},{"issue":"6","key":"ref59","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1582-4934.2011.01258.x","article-title":"Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia","volume":"15","author":"A Carreau","year":"2011","journal-title":"J Cell Mol Med"},{"issue":"10","key":"ref60","doi-asserted-by":"crossref","first-page":"e25839","DOI":"10.1371\/journal.pone.0025839","article-title":"Isolation and characterization of renal erythropoietin-producing cells from genetically produced anemia mice","volume":"6","author":"X Pan","year":"2011","journal-title":"PLoS One"},{"issue":"6","key":"ref61","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1039\/C4MT00329B","article-title":"Back to the metal age: battle for metals at the host-pathogen interface during urinary tract infection","volume":"7","author":"S Subashchandrabose","year":"2015","journal-title":"Metallomics"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/bs.ampbs.2014.08.006","article-title":"Virulence factors of uropathogenic E. coli and their interaction with the host","volume":"65","author":"P Luthje","year":"2014","journal-title":"Adv Microb Physiol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0204471","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T17:28:31Z","timestamp":1589045311000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0204471"}},"subtitle":[],"editor":[{"given":"Fanis","family":"Missirlis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,10,15]]},"references-count":62,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0204471","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,15]]}}}