{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:39:55Z","timestamp":1789159195230,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ferroptosis, an iron\u2010dependent form of programmed cell death driven by toxic lipid peroxide accumulation, plays a critical role in various diseases, making its modulation a promising therapeutic strategy. In this study, we identified several L\u2010type calcium channel blockers as novel inhibitors of ferroptosis. We further elucidated that calcium\u2010dependent activation of PKC\u03b2 drives ferroptosis by phosphorylating two key enzymes, ACSL4 and ALOX15, at multiple sites. We generated phosphorylation\u2010specific antibodies targeting these sites and confirmed their specificity in the context of ferroptosis. Furthermore, upon induction of ferroptosis, the ACSL4\u2010PKC\u03b2\u2010ALOX15 complex relocates to lipid droplets, highlighting a critical role of lipid droplets in ferroptosis. Notably, elevated PKC\u03b2 levels enhance the efficacy of ferroptosis\u2010inducing cancer therapies, while inhibition of the Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    \u2010PKC\u03b2 signaling pathway protects against acute pancreatitis by suppressing ferroptosis. These findings underscore the therapeutic potential of targeting Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    \u2010PKC\u03b2\u2010mediated ferroptosis, offering new avenues for the treatment of cancer and acute pancreatitis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202515768","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T12:20:45Z","timestamp":1769516445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of Calcium\u2010Dependent Lipid Droplets Relocation of ACSL4\u2010PKC\u03b2\u2010ALOX15 Complex Alleviates Ferroptosis and Acute Pancreatitis"],"prefix":"10.1002","volume":"13","author":[{"given":"Guoyuan","family":"Hou","sequence":"first","affiliation":[{"name":"The HIT Center for Life Sciences School of Life Science and Technology Harbin Institute of Technology  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Luan","sequence":"additional","affiliation":[{"name":"The HIT Center for Life Sciences School of Life Science and Technology Harbin Institute of Technology  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Xu","sequence":"additional","affiliation":[{"name":"Hangzhou HuaAn Biotechnology Co., Ltd  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Qin","sequence":"additional","affiliation":[{"name":"The HIT Center for Life Sciences School of Life Science and Technology Harbin Institute of Technology  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Ma","sequence":"additional","affiliation":[{"name":"The HIT Center for Life Sciences School of Life Science and Technology Harbin Institute of Technology  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyuan","family":"He","sequence":"additional","affiliation":[{"name":"The HIT Center for Life Sciences School of Life Science and Technology Harbin Institute of Technology  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Sun","sequence":"additional","affiliation":[{"name":"The HIT Center for Life Sciences School of Life Science and Technology Harbin Institute of Technology  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-4771","authenticated-orcid":false,"given":"Minghui","family":"Gao","sequence":"additional","affiliation":[{"name":"The HIT Center for Life Sciences School of Life Science and Technology Harbin Institute of Technology  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u201000324\u20108"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010024\u201000703\u20105"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.010"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.021"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14344"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.10.042"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010024\u201001407\u20101"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.03.011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010024\u201001425\u20108"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010024\u201007254\u20109"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u201000297\u20102"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010020\u20100461\u20108"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116234"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2239"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2238"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.07.005"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603244113"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.044"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.7b00589"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102732\u20108"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1187366"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2016.95"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2023.102759"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1063"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1081208"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.03.020"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar7607"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010020\u201000691\u2010x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202254746"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2023.102778"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2024.102966"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704183"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.028"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a038802"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2847"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010021\u201000818\u20103"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.524"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx247"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002096"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.05.001"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201044412\u20107"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201006153\u20109"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.01.032"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2014.00117"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.06.011"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/114.3.467"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02890197"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202515768","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202515768","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202515768","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T10:19:05Z","timestamp":1775125145000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202515768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":47,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/advs.202515768"],"URL":"https:\/\/doi.org\/10.1002\/advs.202515768","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]},"assertion":[{"value":"2025-08-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15768"}}