{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:58:20Z","timestamp":1790701100416,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"48","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2025,11,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Widespread human exposure to aluminum (Al) has raised increasing concerns about its effects on neuronal functions since Al\n                    <jats:sup>3+<\/jats:sup>\n                    can cross the blood\u2013brain barrier and accumulate in neuronal cells, especially considering its ionic similarity to ferric iron (Fe\n                    <jats:sup>3+<\/jats:sup>\n                    ), a metal strongly associated with neurodegenerative diseases. In this study, we demonstrate that Al\n                    <jats:sup>3+<\/jats:sup>\n                    affects vesicles in an iron\u2010status\u2010dependent manner in pheochromocytoma (PC12) cells, causing distinct changes under iron\u2010normal, deficient, and overloaded conditions. Al\n                    <jats:sup>3+<\/jats:sup>\n                    competes with Fe\n                    <jats:sup>3+<\/jats:sup>\n                    for transferrin binding and enters cells via transferrin receptor (TfR)\u2010mediated endocytosis, ultimately leading to cellular iron deficiency. This disruption alters dopamine\u2010related proteins and molecular pathways, impairing exocytotic dynamics and reducing the average vesicular transmitter storage. When iron level is overloaded, TfR expression is downregulated to avoid Al\n                    <jats:sup>3+<\/jats:sup>\n                    affecting vesicles. However, supplementation with ferric ammonium citrate (FAC) fails to reverse Al\n                    <jats:sup>3+<\/jats:sup>\n                    \u2010induced iron deficiency due to Al\n                    <jats:sup>3+<\/jats:sup>\n                    simultaneously upregulating TfR, allowing excess Fe\n                    <jats:sup>3+<\/jats:sup>\n                    to further decrease neurotransmitter release. Furthermore, deferoxamine (DFOM), an Fe chelator, destabilizes exocytotic fusion pores, suggesting a potential drawback of chelation therapy. These findings highlight iron dysregulation as a key pathway through which Al\n                    <jats:sup>3+<\/jats:sup>\n                    impairs vesicular function, providing a new insight into how metal ion interactions modulate neurotransmission.\n                  <\/jats:p>","DOI":"10.1002\/anie.202514166","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T09:53:33Z","timestamp":1760003613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Aluminum Exposure Impairs Electrochemically Measured Vesicular Storage and Exocytosis via Iron Homeostasis Dysregulation"],"prefix":"10.1002","volume":"64","author":[{"given":"Shi\u2010Hua","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Chemistry and Molecular Biology University of Gothenburg  Medicinaregatan 19 Gothenburg 41390 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyi","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology University of Gothenburg  Medicinaregatan 19 Gothenburg 41390 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing\u2010Jiu","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Optics and Technology And Environmental Materials and Pollution Control Laboratory Institute of Solid State Physics HFIPS Chinese Academy of Sciences  Hefei 230031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2084-0133","authenticated-orcid":false,"given":"Andrew G.","family":"Ewing","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology University of Gothenburg  Medicinaregatan 19 Gothenburg 41390 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.4c01910"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2007.06.002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7112111"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010004\u20104317\u20103"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010191140"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2014.02.004"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.22.9024"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010\u20108545(02)00038\u20103"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202200716"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(03)00353\u20103"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphc.200900647"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn900040e"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201700095"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.23.10754"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202315681"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570\u2010017\u20100048"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201504839"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.7.2424"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1910859116"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth782"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c02013"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20103495(96)79652\u20102"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(77)90005\u20101"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327107083973"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(90)90196\u2010I"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640\u2010020\u201000319\u20105"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/09603271221136206"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.8.3471"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb400665f"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5351\u201012.2013"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2007.02.001"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2006.04.015"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010007\u20109358\u20101"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014\u20105793(99)01533\u20101"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010\u20108545(02)00078\u20104"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/15376516.2022.2053254"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523\u20101755.2001.059002746.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9061456"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2011.08.016"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1211\/0022357991772231"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.111926"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2946"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202514166","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202514166","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202514166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:06:25Z","timestamp":1790697985000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202514166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":42,"journal-issue":{"issue":"48","published-print":{"date-parts":[[2025,11,24]]}},"alternative-id":["10.1002\/anie.202514166"],"URL":"https:\/\/doi.org\/10.1002\/anie.202514166","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,9]]},"assertion":[{"value":"2025-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202514166"}}