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However, its role in autophagy and ADCD is not fully understood. Here, we demonstrated that amino acid deprivation (AA[\u2212]) in murine lymphoid WR19L cells promoted the accumulation of ceramide at phagophores and autophagy, resulting in ADCD. Control of ceramide production by sphingomyelin synthase 1 and neutral sphingomyelinase 2 altered cell fate by regulating AA(\u2212)\u2010induced autophagy and ADCD. In\u00a0vitro reconstruction analysis of phosphatidylethanolamine (PE) binding to microtubule\u2010associated protein\u20101 light chain\u20103 (LC3), a key step in phagophore formation leading to autophagic flux, revealed that ceramide promoted the PE lipidation of LC3. These results suggest that ceramide promotes autophagosome formation by enhancing PE lipidation of LC3, leading to excess autophagy and ADCD. This study highlights novel insights into the ceramide\/sphingomyelin balance at autophagy\u2010related membranes, which controls the switch on autophagy and ADCD through enhanced lipidation of LC3.<\/jats:p>","DOI":"10.1096\/fj.202500348r","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T10:04:19Z","timestamp":1748253859000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phagophore Ceramide Promotes\n                    <scp>LC3<\/scp>\n                    Lipidation and Autophagy in T\u2010Lymphoid Cell Death"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-8285","authenticated-orcid":false,"given":"Makoto","family":"Taniguchi","sequence":"first","affiliation":[{"name":"Medical Research Institute Kanazawa Medical University  Uchinada Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Nagaya","sequence":"additional","affiliation":[{"name":"Research Institute for Bioresources and Biotechnology Ishikawa Prefectural University  Nonoichi\u2010shi Ishikawa Japan"},{"name":"R&amp;D Department, Shalom Co., Ltd.  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