{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:13:01Z","timestamp":1790251981901,"version":"4.1.0"},"reference-count":70,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK085035"],"award-info":[{"award-number":["DK085035"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["ES025661"],"award-info":[{"award-number":["ES025661"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK110858"],"award-info":[{"award-number":["DK110858"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"crossref","award":["Intramural"],"award-info":[{"award-number":["Intramural"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000015","name":"Department of Energy","doi-asserted-by":"crossref","award":["DE-AC02-06CH11357"],"award-info":[{"award-number":["DE-AC02-06CH11357"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Japan Synchrotron Radiation Research Institute","award":["2017A0074"],"award-info":[{"award-number":["2017A0074"]}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2019,8,24]]},"abstract":"<jats:p>\n                    Free heme is cytotoxic as exemplified by hemolytic diseases and genetic deficiencies in heme recycling and detoxifying pathways. Thus, intracellular accumulation of heme has not been observed in mammalian cells to date. Here we show that mice deficient for the heme transporter SLC48A1 (also known as HRG1) accumulate over ten-fold excess heme in reticuloendothelial macrophage lysosomes that are 10 to 100 times larger than normal. Macrophages tolerate these high concentrations of heme by crystallizing them into hemozoin, which heretofore has only been found in blood-feeding organisms.\n                    <jats:italic>SLC48A1<\/jats:italic>\n                    deficiency results in impaired erythroid maturation and an inability to systemically respond to iron deficiency. Complete heme tolerance requires a fully-operational heme degradation pathway as haplo insufficiency of\n                    <jats:italic>HMOX1<\/jats:italic>\n                    combined with\n                    <jats:italic>SLC48A1<\/jats:italic>\n                    inactivation causes perinatal lethality demonstrating synthetic lethal interactions between heme transport and degradation. Our studies establish the formation of hemozoin by mammals as a previously unsuspected heme tolerance pathway.\n                  <\/jats:p>","DOI":"10.7554\/elife.49503","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T20:31:57Z","timestamp":1569875517000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.49503","source":"Crossref","is-referenced-by-count":53,"title":["Hemozoin produced by mammals confers heme tolerance"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-7534","authenticated-orcid":true,"given":"Rini H","family":"Pek","sequence":"first","affiliation":[{"name":"Department of Animal and Avian Sciences, University of Maryland","place":["College Park, United States"]},{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland","place":["College Park, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0969-5748","authenticated-orcid":true,"given":"Xiaojing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Animal and Avian Sciences, University of Maryland","place":["College Park, United States"]},{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland","place":["College Park, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Rietzschel","sequence":"additional","affiliation":[{"name":"Department of Animal and Avian Sciences, University of Maryland","place":["College Park, United States"]},{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland","place":["College Park, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Animal and Avian Sciences, University of Maryland","place":["College Park, United States"]},{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland","place":["College Park, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Utah School of Medicine","place":["Salt Lake City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Nishibori","sequence":"additional","affiliation":[{"name":"Faculty of Pure and Applied Sciences, University of Tsukuba","place":["Tsukuba, Japan"]},{"name":"Tsukuba Research Center for Energy Materials Science, University of Tsukaba","place":["Tsukaba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Animal and Avian Sciences, University of Maryland","place":["College Park, United States"]},{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland","place":["College Park, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Simmons","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"Jagadeesh","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3140-8362","authenticated-orcid":true,"given":"Hiroshi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"RIKEN SPring-8 Center, Sayo","place":["Hyogo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Zahidul","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania","place":["Philadelphia, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Garrett","sequence":"additional","affiliation":[{"name":"NHGRI Embryonic Stem Cell and Transgenic Mouse Core, National Human Genome Research Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malay","family":"Haldar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania","place":["Philadelphia, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Ralle","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics, Oregon Health and Science University","place":["Portland, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Utah School of Medicine","place":["Salt Lake City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Bodine","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0045-0610","authenticated-orcid":true,"given":"Iqbal","family":"Hamza","sequence":"additional","affiliation":[{"name":"Department of Animal and Avian Sciences, University of Maryland","place":["College Park, United States"]},{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland","place":["College Park, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"W147","DOI":"10.1093\/nar\/gkw419","article-title":"Heatmapper: web-enabled heat mapping for all","volume":"44","author":"Babicki","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086847","article-title":"Lysosome transport as a function of lysosome diameter","volume":"9","author":"Bandyopadhyay","year":"2014","journal-title":"PLOS ONE"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.1594","article-title":"Pyridine hemochromagen assay for determining the concentration of heme in purified protein solutions","volume":"5","author":"Barr","year":"2015","journal-title":"Bio-Protocol"},{"key":"bib4","first-page":"135","article-title":"Synergistic and antagonistic interactions between haemozoin and bacterial endotoxin on human and mouse macrophages","volume":"45","author":"Basilico","year":"2003","journal-title":"Parassitologia"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1053\/j.seminhematol.2009.06.004","article-title":"Recycling iron in normal and pathological states","volume":"46","author":"Beaumont","year":"2009","journal-title":"Seminars in Hematology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/jbmr.2036","article-title":"Effects of weight-bearing activities on bone mineral content and density in children and adolescents: a meta-analysis","volume":"29","author":"Behringer","year":"2014","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"16644","DOI":"10.1074\/jbc.M116.727248","article-title":"The activity of menkes disease protein ATP7A is essential for redox balance in mitochondria","volume":"291","author":"Bhattacharjee","year":"2016","journal-title":"Journal of Biological Chemistry"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0166-6851(00)00365-0","article-title":"Haemoproteus and Schistosoma synthesize heme polymers similar to Plasmodium hemozoin and \u03b2-hematin","volume":"113","author":"Chen","year":"2001","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"17413","DOI":"10.1073\/pnas.0909296106","article-title":"Resolving the distinct stages in erythroid differentiation based on dynamic changes in membrane protein expression during erythropoiesis","volume":"106","author":"Chen","year":"2009","journal-title":"PNAS"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1017\/S1551929515000401","article-title":"The bionanoprobe: synchrotron-based hard X-ray fluorescence microscopy for 2D\/3D trace element mapping","volume":"23","author":"Chen","year":"2015","journal-title":"Microscopy Today"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1016\/j.bbagen.2014.02.009","article-title":"Malarial hemozoin: from target to tool","volume":"1840","author":"Coronado","year":"2014","journal-title":"Biochimica Et Biophysica Acta (BBA) - General Subjects"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.yexcr.2005.07.002","article-title":"A physiological model to study iron recycling in macrophages","volume":"310","author":"Delaby","year":"2005","journal-title":"Experimental Cell Research"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042199","article-title":"Subcellular localization of iron and heme metabolism related proteins at early stages of erythrophagocytosis","volume":"7","author":"Delaby","year":"2012","journal-title":"PLOS ONE"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-11-166","article-title":"Improved methods for haemozoin quantification in tissues yield organ-and parasite-specific information in malaria-infected mice","volume":"11","author":"Deroost","year":"2012","journal-title":"Malaria Journal"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1136\/gut.51.5.648","article-title":"Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice","volume":"51","author":"Dupic","year":"2002","journal-title":"Gut"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"E4110","DOI":"10.1073\/pnas.1405023111","article-title":"Hemolysis-induced lethality involves inflammasome activation by heme","volume":"111","author":"Dutra","year":"2014","journal-title":"PNAS"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1021\/bi0013501","article-title":"The mechanism of beta-hematin formation in acetate solution. Parallels between hemozoin formation and biomineralization processes","volume":"40","author":"Egan","year":"2001","journal-title":"Biochemistry"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.molbiopara.2007.11.005","article-title":"Haemozoin formation","volume":"157","author":"Egan","year":"2008","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"609","DOI":"10.2174\/156652408786241384","article-title":"The role of oxidative stress in hemolytic Anemia","volume":"8","author":"Fibach","year":"2008","journal-title":"Current Molecular Medicine"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1146\/annurev.micro.51.1.97","article-title":"Hemoglobin metabolism in the malaria parasite plasmodium falciparum","volume":"51","author":"Francis","year":"1997","journal-title":"Annual Review of Microbiology"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1038\/srep12940","article-title":"Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates","volume":"5","author":"Franken","year":"2015","journal-title":"Scientific Reports"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1159\/000336423","article-title":"Macrophages and systemic iron homeostasis","volume":"4","author":"Ganz","year":"2012","journal-title":"Journal of Innate Immunity"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.bbamcr.2006.03.014","article-title":"Regulation of iron acquisition and iron distribution in mammals","volume":"1763","author":"Ganz","year":"2006","journal-title":"Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1016\/j.bbamcr.2012.01.014","article-title":"Hepcidin and iron homeostasis","volume":"1823","author":"Ganz","year":"2012","journal-title":"Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1182\/asheducation-2009.1.73","article-title":"Drug-induced immune hemolytic anemia","volume":"2009","author":"Garratty","year":"2009","journal-title":"Hematology"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/j.cell.2014.01.069","article-title":"Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages","volume":"156","author":"Haldar","year":"2014","journal-title":"Cell"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1007\/s00436-006-0313-x","article-title":"Hemozoin biocrystallization in plasmodium falciparum and the antimalarial activity of crystallization inhibitors","volume":"100","author":"Hempelmann","year":"2007","journal-title":"Parasitology Research"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/sj.emboj.7601511","article-title":"LAMP proteins are required for fusion of lysosomes with phagosomes","volume":"26","author":"Huynh","year":"2007","journal-title":"The EMBO Journal"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1083\/jcb.201507112","article-title":"The position of lysosomes within the cell determines their luminal pH","volume":"212","author":"Johnson","year":"2016","journal-title":"The Journal of Cell Biology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1182\/blood-2014-05-516252","article-title":"Molecular liaisons between erythropoiesis and iron metabolism","volume":"124","author":"Kautz","year":"2014","journal-title":"Blood"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1126\/science.1151133","article-title":"A heme export protein is required for red blood cell differentiation and iron homeostasis","volume":"319","author":"Keel","year":"2008","journal-title":"Science"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00073","article-title":"From the cradle to the grave: the role of macrophages in erythropoiesis and erythrophagocytosis","volume":"8","author":"Klei","year":"2017","journal-title":"Frontiers in Immunology"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"4191","DOI":"10.1182\/blood-2003-04-1250","article-title":"Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages","volume":"102","author":"Knutson","year":"2003","journal-title":"Blood"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1073\/pnas.0409409102","article-title":"Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin","volume":"102","author":"Knutson","year":"2005","journal-title":"PNAS"},{"key":"bib35","doi-asserted-by":"publisher","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":"Kovtunovych","year":"2010","journal-title":"Blood"},{"key":"bib36","doi-asserted-by":"publisher","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":"Kovtunovych","year":"2014","journal-title":"Blood"},{"key":"bib37","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.19804","article-title":"An essential cell-autonomous role for hepcidin in cardiac iron homeostasis","volume":"5","author":"Lakhal-Littleton","year":"2016","journal-title":"eLife"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00077","article-title":"Heme cytotoxicity and the pathogenesis of immune-mediated inflammatory diseases","volume":"3","author":"Larsen","year":"2012","journal-title":"Frontiers in Pharmacology"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1088\/0143-0807\/23\/1\/304","article-title":"Demonstration of the exponential decay law using beer froth","volume":"23","author":"Leike","year":"2002","journal-title":"European Journal of Physics"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.1182\/blood-2004-02-0703","article-title":"BMP4 and Madh5 regulate the erythroid response to acute Anemia","volume":"105","author":"Lenox","year":"2005","journal-title":"Blood"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003772","article-title":"Age-Related reference intervals of the main biochemical and hematological parameters in C57BL\/6J, 129sv\/EV and C3H\/HeJ mouse strains","volume":"3","author":"Mazzaccara","year":"2008","journal-title":"PLOS ONE"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1146\/annurev.bi.55.070186.003311","article-title":"Acidification of the endocytic and exocytic pathways","volume":"55","author":"Mellman","year":"1986","journal-title":"Annual Review of Biochemistry"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"4617","DOI":"10.3748\/wjg.15.4617","article-title":"An update on iron physiology","volume":"15","author":"Mu\u00f1oz","year":"2009","journal-title":"World Journal of Gastroenterology"},{"key":"bib44","doi-asserted-by":"publisher","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":"Nemeth","year":"2004","journal-title":"Science"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1016\/S0022-3697(01)00164-0","article-title":"The large Debye\u2013Scherrer camera installed at SPring-8 BL02B2 for charge density studies","volume":"62","author":"Nishibori","year":"2001","journal-title":"Journal of Physics and Chemistry of Solids"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1107\/S0108767306047210","article-title":"Accurate structure factors and experimental charge densities from synchrotron X-ray powder diffraction data at SPring-8","volume":"63","author":"Nishibori","year":"2007","journal-title":"Acta Crystallographica Section A"},{"key":"bib47","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00666","article-title":"Infection-related hemolysis and susceptibility to Gram-negative bacterial co-infection","volume":"6","author":"Orf","year":"2015","journal-title":"Frontiers in Microbiology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1182\/blood-2008-03-147892","article-title":"Maintenance of the BMP4-dependent stress erythropoiesis pathway in the murine spleen requires hedgehog signaling","volume":"113","author":"Perry","year":"2009","journal-title":"Blood"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"10919","DOI":"10.1073\/pnas.94.20.10919","article-title":"Heme oxygenase 1 is required for mammalian iron reutilization","volume":"94","author":"Poss","year":"1997","journal-title":"PNAS"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"10925","DOI":"10.1073\/pnas.94.20.10925","article-title":"Reduced stress defense in heme oxygenase 1-deficient cells","volume":"94","author":"Poss","year":"1997","journal-title":"PNAS"},{"key":"bib51","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1182\/blood.V94.9.3185","article-title":"Importance of Anemia and transferrin levels in the regulation of intestinal iron absorption in hypotransferrinemic mice","volume":"94","author":"Raja","year":"1999","journal-title":"Blood"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1038\/nature06934","article-title":"Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins","volume":"453","author":"Rajagopal","year":"2008","journal-title":"Nature"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/978-1-62703-523-1_7","article-title":"Detection of pyroptosis by measuring released lactate dehydrogenase activity","volume":"1040","author":"Rayamajhi","year":"2013","journal-title":"Methods in Molecular Biology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/0925-4439(93)90089-J","article-title":"Phagocytosis of P. falciparum malarial pigment hemozoin by human monocytes inactivates monocyte protein kinase C","volume":"1181","author":"Schwarzer","year":"1993","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"15837","DOI":"10.1073\/pnas.0903419106","article-title":"Heme oxygenase-1 affords protection against noncerebral forms of severe malaria","volume":"106","author":"Seixas","year":"2009","journal-title":"PNAS"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.micinf.2010.07.001","article-title":"Innate inflammatory response to the malarial pigment hemozoin","volume":"12","author":"Shio","year":"2010","journal-title":"Microbes and Infection"},{"key":"bib57","doi-asserted-by":"publisher","DOI":"10.1002\/0471140856.tx0803s00","article-title":"Measurement of heme concentration","volume":"8","author":"Sinclair","year":"2001","journal-title":"Current Protocols in Toxicology"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1073\/pnas.88.2.325","article-title":"An iron-carboxylate bond links the heme units of malaria pigment","volume":"88","author":"Slater","year":"1991","journal-title":"PNAS"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1097\/MOH.0b013e3280de2bf1","article-title":"Molecular insights into stress erythropoiesis","volume":"14","author":"Socolovsky","year":"2007","journal-title":"Current Opinion in Hematology"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"5960","DOI":"10.1073\/pnas.0900808106","article-title":"Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo","volume":"106","author":"Soe-Lin","year":"2009","journal-title":"PNAS"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.exphem.2010.04.003","article-title":"Both Nramp1 and DMT1 are necessary for efficient macrophage iron recycling","volume":"38","author":"Soe-Lin","year":"2010","journal-title":"Experimental Hematology"},{"key":"bib62","first-page":"900","article-title":"Iron balance in the mouse","volume":"24","author":"Sorbie","year":"1974","journal-title":"Laboratory Animal Science"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"3342","DOI":"10.1021\/cg200410b","article-title":"The role of the four stereoisomers of the heme Fe\u2013O Cyclic Dimer in the Crystalline Phase Behavior of Synthetic Hemozoin: Relevance to Native Hemozoin Crystallization","volume":"11","author":"Straas\u00f8","year":"2011","journal-title":"Crystal Growth & Design"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1038\/nm.4146","article-title":"On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver","volume":"22","author":"Theurl","year":"2016","journal-title":"Nature Medicine"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/1756-3305-3-108","article-title":"Heme and blood-feeding parasites: friends or foes?","volume":"3","author":"Toh","year":"2010","journal-title":"Parasites & Vectors"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1051\/jp4:20030160","article-title":"MAPS : a set of software tools for analysis and visualization of 3D X-ray fluorescence data sets","volume":"104","author":"Vogt","year":"2003","journal-title":"Journal De Physique IV"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1038\/ng2059","article-title":"Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice","volume":"39","author":"Wang","year":"2007","journal-title":"Nature Genetics"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.cmet.2013.01.005","article-title":"HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis","volume":"17","author":"White","year":"2013","journal-title":"Cell Metabolism"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1309\/LMF28S2GIMXNWHMM","article-title":"The molecular biology of human iron metabolism","volume":"45","author":"Winter","year":"2014","journal-title":"Laboratory Medicine"},{"key":"bib70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007665","article-title":"Hrg1 promotes heme-iron recycling during hemolysis in the zebrafish kidney","volume":"14","author":"Zhang","year":"2018","journal-title":"PLOS Genetics"}],"updated-by":[{"DOI":"10.7554\/elife.93253","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T00:00:00Z","timestamp":1697760000000}}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/49503\/elife-49503-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/49503\/elife-49503-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/49503","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T10:01:15Z","timestamp":1697796075000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/49503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,1]]},"references-count":70,"alternative-id":["10.7554\/eLife.49503"],"URL":"https:\/\/doi.org\/10.7554\/elife.49503","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.49503.020","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.49503.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.49503.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.49503.019","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/629725","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,1]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e49503"}}