{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:56:24Z","timestamp":1790661384844,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2017\/25\/N\/NZ3\/01957"],"award-info":[{"award-number":["2017\/25\/N\/NZ3\/01957"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The critical function of ferroportin (Fpn) in maintaining iron homeostasis requires complex and multilevel control of its expression. Besides iron-dependent cellular and systemic control of Fpn expression, other metals also seem to be involved in regulating the Fpn gene. Here, we found that copper loading significantly enhanced Fpn transcription in an Nrf2-dependent manner in primary bone-marrow-derived macrophages (BMDMs). However, prolonged copper loading resulted in decreased Fpn protein abundance. Moreover, CuCl2 treatment induced Fpn expression in RAW 264.7 macrophages at both the mRNA and protein level. These data suggest that cell-type-specific regulations have an impact on Fpn protein stability after copper loading. Transcriptional suppression of Fpn after lipopolysaccharide (LPS) treatment contributes to increased iron storage inside macrophages and may result in anemia of inflammation. Here, we observed that in both primary BMDMs and RAW 264.7 macrophages, LPS treatment significantly decreased Fpn mRNA levels, but concomitant CuCl2 stimulation counteracted the transcriptional suppression of Fpn and restored its expression to the control level. Overall, we show that copper loading significantly enhances Fpn transcription in macrophages, while Fpn protein abundance in response to CuCl2 treatment, depending on macrophage type and factors specific to the macrophage population, can influence Fpn regulation in response to copper loading.<\/jats:p>","DOI":"10.3390\/cells10092259","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T08:42:32Z","timestamp":1630399352000},"page":"2259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Role of Copper in the Regulation of Ferroportin Expression in Macrophages"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-6853","authenticated-orcid":false,"given":"Aneta","family":"Jo\u0144czy","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6706-0882","authenticated-orcid":false,"given":"Rafa\u0142","family":"Mazgaj","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Smuda","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"\u017belazowska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5869-7670","authenticated-orcid":false,"given":"Zuzanna","family":"Kope\u0107","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142 Rados\u0142aw","family":"Starzy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Lipi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.cmet.2015.09.006","article-title":"Review Ironing out Ferroportin","volume":"22","author":"Drakesmith","year":"2015","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/ajh.26001","article-title":"Cell-type-specific insights into iron regulatory processes","volume":"96","author":"Silvestri","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S0168-8278(03)00408-2","article-title":"The role of the iron responsive element in the control of ferroportin1\/IREG1\/MTP1 gene expression","volume":"39","author":"Lymboussaki","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_4","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":"Nemeth","year":"2004","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.3324\/haematol.2009.020123","article-title":"Heme controls ferroportin1 (FPN1) transcription involving Bach1, Nrf2 and a MARE\/ARE sequence motif at position -7007 of the FPN1 promoter","volume":"95","author":"Marro","year":"2010","journal-title":"Haematologica"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1042\/BJ20071474","article-title":"Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages: Early mRNA induction by haem, followed by iron-dependent protein expression","volume":"411","author":"Delaby","year":"2008","journal-title":"Biochem. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3945\/jn.108.094052","article-title":"Iron Loading Increases Ferroportin Heterogeneous Nuclear RNA and mRNA Levels in Murine","volume":"139","author":"Aydemir","year":"2009","journal-title":"J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1152\/ajplung.00114.2002","article-title":"Iron increases expression of iron-export protein MTP1 in lung cells","volume":"283","author":"Yang","year":"2002","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4657","DOI":"10.1182\/blood-2010-04-278614","article-title":"Induction of FPN1 transcription by MTF-1 reveals a role for ferroportin in transition metal efflux","volume":"116","author":"Troadec","year":"2010","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1073\/pnas.0306622101","article-title":"Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux","volume":"101","author":"Chung","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1753-4887.2010.00271.x","article-title":"Metabolic crossroads of iron and copper","volume":"68","author":"Collins","year":"2013","journal-title":"Nutr. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-017-1141-8","article-title":"Immune modulation of some autoimmune diseases: The critical role of macrophages and neutrophils in the innate and adaptive immunity","volume":"15","author":"Navegantes","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1039\/C4MT00104D","article-title":"Macrophages: Central regulators of iron balance","volume":"6","author":"Gammella","year":"2014","journal-title":"Metallomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3389\/fimmu.2017.00498","article-title":"Iron- and hepcidin-independent downregulation of the iron exporter ferroportin in macrophages during Salmonella infection","volume":"8","author":"Willemetz","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1182\/blood-2018-06-856500","article-title":"Anemia of inflammation","volume":"133","author":"Weiss","year":"2019","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1053\/j.seminhematol.2009.06.001","article-title":"Iron Sequestration and Anemia of Inflammation","volume":"46","author":"Ganz","year":"2009","journal-title":"Semin. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/jlb.60.1.8","article-title":"Endotoxin signal transduction in macrophages","volume":"60","author":"Sweet","year":"1996","journal-title":"J. Leukoc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4148","DOI":"10.1182\/blood-2002-08-2459","article-title":"Cytokine-mediated regulation of iron transport in human monocytic cells","volume":"101","author":"Ludwiczek","year":"2003","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.abb.2011.02.001","article-title":"Nrf2 regulates ferroportin 1-mediated iron efflux and counteracts lipopolysaccharide-induced ferroportin 1 mRNA suppression in macrophages","volume":"508","author":"Harada","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/jn\/138.2.305","article-title":"Associations of Dietary and Serum Copper with Inflammation, Oxidative Stress, and Metabolic Variables in Adults","volume":"138","author":"Bo","year":"2008","journal-title":"J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.mad.2015.01.004","article-title":"Serum copper to zinc ratio: Relationship with aging and health status","volume":"151","author":"Malavolta","year":"2015","journal-title":"Mech. Ageing Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1042\/BJ20112180","article-title":"Copper redistribution in murine macrophages in response to Salmonella infection","volume":"444","author":"Achard","year":"2012","journal-title":"Biochem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33949","DOI":"10.1074\/jbc.M109.070201","article-title":"A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity","volume":"284","author":"White","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ray, A., and Dittel, B.N. (2010). Isolation of mouse peritoneal cavity cells. J. Vis. Exp., 9\u201311.","DOI":"10.3791\/1488"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.3324\/haematol.2009.019992","article-title":"Lipid raft-dependent endocytosis: A new route for hepcidin-mediated regulation of ferroportin in macrophages","volume":"95","author":"Auriac","year":"2010","journal-title":"Haematologica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.bcmd.2011.11.005","article-title":"Immune cells and hepatocytes express glycosylphosphatidylinositol-anchored ceruloplasmin at their cell surface","volume":"48","author":"Marques","year":"2012","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1158\/1541-7786.MCR-07-0108","article-title":"Identification of flotillin-2, a major protein on lipid rafts, as a novel target of p53 family members","volume":"6","author":"Sasaki","year":"2008","journal-title":"Mol. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1083\/jcb.141.4.929","article-title":"Lipid domain structure of the plasma membrane revealed by patching of membrane components","volume":"141","author":"Harder","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1042\/BST20150044","article-title":"Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress","volume":"43","author":"Mutter","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.bcmd.2005.04.006","article-title":"Regulation of hepcidin and ferroportin expression by lipopolysaccharide in splenic macrophages","volume":"35","author":"Liu","year":"2005","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0005-2728(96)00022-9","article-title":"The ferritins: Molecular properties, iron storage function and cellular regulation","volume":"1275","author":"Harrison","year":"1996","journal-title":"Biochim. Biophys. Acta-Bioenerg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-59898-0","article-title":"H-Ferritin is essential for macrophages\u2019 capacity to store or detoxify exogenously added iron","volume":"10","author":"Mesquita","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1126\/science.2452485","article-title":"Iron-responsive elements: Regulatory RNA sequences that control mRNA levels and translation","volume":"240","author":"Casey","year":"1988","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1039\/C4MT00164H","article-title":"Iron regulatory proteins and their role in controlling iron metabolism","volume":"7","year":"2015","journal-title":"Metallomics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1189\/jlb.0407216","article-title":"Expression and localization of hepcidin in macrophages: A role in host defense against tuberculosis","volume":"82","author":"Sow","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S1097-2765(00)80425-6","article-title":"A Novel Duodenal Iron-Regulated Transporter, IREG1, Implicated in the Basolateral Transfer of Iron to the Circulation","volume":"5","author":"Mckie","year":"2000","journal-title":"Mol. Cell."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1182\/blood.V94.7.2383.419k20_2383_2389","article-title":"Regulation of iron metabolism in murine J774 macrophages: Role of nitric oxide-dependent and -independent pathways following activation with gamma interferon and lipopolysaccharide","volume":"94","author":"Mulero","year":"1999","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/713609210","article-title":"Iron metabolism in the reticuloendothelial system","volume":"38","author":"Knutson","year":"2003","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1152\/ajpcell.00348.2013","article-title":"Functional properties of human ferroportin, a cellular iron exporter reactive also with cobalt and zinc","volume":"306","author":"Mitchell","year":"2014","journal-title":"Am. J. Physiol Cell Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1016\/j.bbamcr.2012.01.005","article-title":"The taste of heavy metals: Gene regulation by MTF-1","volume":"1823","author":"Lindert","year":"2012","journal-title":"Biochim. Biophys. Acta-Mol. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ha, J.H., Doguer, C., Wang, X., Flores, S.R., and Collins, J.F. (2016). High-iron consumption impairs growth and causes copper-deficiency anemia in weanling Sprague-Dawley rats. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161033"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/MCG.0b013e3181dc25f7","article-title":"Hepatic iron overload or cirrhosis may occur in acquired copper deficiency and is likely mediated by hypoceruloplasminemia","volume":"45","author":"Thackeray","year":"2011","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.bbadis.2016.11.005","article-title":"Nrf2 signaling pathway: Pivotal roles in inflammation","volume":"1863","author":"Ahmed","year":"2017","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1042\/BSR20130014","article-title":"Metal ions in macrophage antimicrobial pathways: Emerging roles for zinc and copper","volume":"33","author":"Stafford","year":"2013","journal-title":"Biosci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nrmicro2836","article-title":"Nutritional immunity: Transition metals at the pathogen-host interface","volume":"10","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1189\/jlb.1107781","article-title":"The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome","volume":"84","author":"Sow","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"39786","DOI":"10.1074\/jbc.M201485200","article-title":"Regulation of reticuloendothelial iron transporter MTP1 (Slc11a3) by inflammation","volume":"277","author":"Yang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-04446-8","article-title":"The hepcidin-ferroportin axis controls the iron content of Salmonella-containing vacuoles in macrophages","volume":"9","author":"Lim","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/j.bbadis.2017.02.020","article-title":"Copper therapy reduces intravascular hemolysis and derepresses ferroportin in mice with mosaic mutation (Atp7amo-ms): An implication for copper-mediated regulation of the Slc40a1 gene expression","volume":"1863","author":"Lenartowicz","year":"2017","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"27144","DOI":"10.1074\/jbc.M301988200","article-title":"Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system","volume":"278","author":"Jeong","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41584-020-0372-x","article-title":"Mechanisms of action of hydroxychloroquine and chloroquine: Implications for rheumatology","volume":"16","author":"Schrezenmeier","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.devcel.2014.04.033","article-title":"Wilson Disease Protein ATP7B Utilizes Lysosomal Exocytosis to Maintain Copper Homeostasis","volume":"29","author":"Polishchuk","year":"2014","journal-title":"Dev. Cell."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1620\/tjem.172.355","article-title":"Impaired Lysosomal Rat Biliary Excretion of Copper and Enzymes in Long-Evans cinnamon","volume":"172","author":"Abe","year":"1994","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep42225","article-title":"Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis","volume":"7","author":"Andreu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2014.00514","article-title":"From monocytes to M1\/M2 macrophages: Phenotypical vs. functional differentiation","volume":"5","author":"Italiani","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep35234","article-title":"Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1\/M2 marker expression-Implications for atherosclerosis research","volume":"6","author":"Bisgaard","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_57","first-page":"1","article-title":"Evaluation of the immunomodulatory effects of cobalt, copper and magnesium ions in a pro inflammatory environment","volume":"11","author":"Delgado","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/eji.200939889","article-title":"Differential regulation of iron homeostasis during human macrophage polarized activation","volume":"40","author":"Recalcati","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.3324\/haematol.2010.023879","article-title":"Polarization dictates iron handling by inflammatory and alternatively activated macrophages","volume":"95","author":"Corna","year":"2010","journal-title":"Haematologica"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrm1571","article-title":"Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling","volume":"6","author":"Wrana","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/35036052","article-title":"Lipid rafts and signal transduction","volume":"1","author":"Simons","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1194\/jlr.TR119000383","article-title":"The ins and outs of lipid rafts: Functions in intracellular cholesterol homeostasis, microparticles, and cell membranes","volume":"61","author":"Ouweneel","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"8343","DOI":"10.1074\/jbc.M607496200","article-title":"High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease","volume":"282","author":"Huster","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"21899","DOI":"10.1074\/jbc.M109.019521","article-title":"Paradoxical condensation of copper with elevated \u03b2-amyloid in lipid rafts under cellular copper deficiency conditions: Implications for Alzheimer disease","volume":"284","author":"Hung","year":"2009","journal-title":"J. Biol. Chem."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/9\/2259\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:53:22Z","timestamp":1760165602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/9\/2259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":64,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["cells10092259"],"URL":"https:\/\/doi.org\/10.3390\/cells10092259","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]}}}