{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:50:15Z","timestamp":1792651815819,"version":"4.5.0"},"reference-count":69,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"13","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,3,28]]},"abstract":"<jats:p>\n                    The role of canonical autophagy in controlling\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb), referred to as xenophagy, is understood to involve targeting Mtb to autophagosomes, which subsequently fuse with lysosomes for degradation. Here, we found that Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leakage after Mtb phagosome damage in human macrophages is the signal that triggers autophagy-related protein 8\/microtubule-associated proteins 1A\/1B light chain 3 (ATG8\/LC3) lipidation. Unexpectedly, ATG8\/LC3 lipidation did not target Mtb to lysosomes, excluding the canonical xenophagy. Upon Mtb phagosome damage, the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leakage\u2013dependent ATG8\/LC3 lipidation occurred on multiple membranes instead of single or double membranes excluding the noncanonical autophagy pathways. Mechanistically, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leakage from the phagosome triggered the recruitment of the V-ATPase\u2013ATG16L1 complex independently of FIP200, ATG13, and proton gradient disruption. Furthermore, the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leakage\u2013dependent ATG8\/LC3 lipidation limited Mtb phagosome damage and restricted Mtb replication. Together, we uncovered Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leakage as the key signal that triggers ATG8\/LC3 lipidation on multiple membranes to mitigate Mtb phagosome damage.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adt3311","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T14:45:32Z","timestamp":1743000332000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":24,"title":["<i>Mycobacterium tuberculosis<\/i>\n                    phagosome Ca\n                    <sup>2+<\/sup>\n                    leakage triggers multimembrane ATG8\/LC3 lipidation to restrict damage in human macrophages"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2186-7717","authenticated-orcid":true,"given":"Di","family":"Chen","sequence":"first","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-8545","authenticated-orcid":true,"given":"Antony","family":"Fearns","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3199-0337","authenticated-orcid":true,"given":"Maximiliano G.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.21.5720"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2024.168532"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06421"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.03.020"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.056"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.01.041"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01632.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201796697"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.222984"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-020-0141-7"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.171"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.72328"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2312306120"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202302067"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202303078"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.261031"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01329-z"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202105112"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.4161\/15548627.2014.984277"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.07.003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.038"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01354-6"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01335-9"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1707792114"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.252973"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.3.599"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(07)00565-9"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.2.693"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.09.001"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.10.006"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201603040"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.72.4.1973"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.4451"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e08-12-1248"},{"key":"e_1_3_2_36_2","first-page":"5224","article-title":"Dynamic association of the ULK1 complex with omegasomes during autophagy induction","volume":"126","author":"Karanasios E.","year":"2013","unstructured":"E. 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