{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:34:01Z","timestamp":1786707241701,"version":"build-2736575974"},"reference-count":59,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["2508\u201008462"],"award-info":[{"award-number":["2508\u201008462"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["RGS\\R1\\231207"],"award-info":[{"award-number":["RGS\\R1\\231207"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W01632X\/1"],"award-info":[{"award-number":["MR\/W01632X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>\n                    Naked mole\u2010rats (NMRs,\n                    <jats:italic>Heterocephalus glaber<\/jats:italic>\n                    ) display unusual longevity and resistance to age\u2010related decline, and accumulating evidence suggests that their autophagy\u2013lysosome pathway (ALP) is regulated differently from that of conventional mammalian models. However, most studies in NMR cells have relied on static biochemical or ultrastructural readouts, leaving the dynamic organisation of autophagy in living cells poorly defined. Here, we establish a stable tandem fluorescent autophagy reporter in NMR skin fibroblasts using an mCherry\u2013EGFP\u2013LC3\n                    <jats:sup>NMR<\/jats:sup>\n                    construct to enable live\u2010cell, single\u2010cell resolution analysis of ALP dynamics. Under basal conditions, NMR skin fibroblasts exhibit a greater abundance of LC3\u2010positive structures than HeLa cells, together with a mixed population of autophagosomes and autolysosomes, indicating a distinct steady\u2010state organisation of the ALP. Chloroquine (CQ)\u2010induced lysosomal stress caused the expected accumulation of LC3\u2010positive structures but also triggered the formation of large cytoplasmic vacuoles in NMR skin fibroblasts. Importantly, this vacuolation was not associated with acute cytotoxicity and progressively resolved following CQ removal, accompanied by reorganisation of LC3\u2010positive compartments and recovery of lysosomal acidity. Electron microscopy showed that CQ\u2010induced vacuoles are membrane\u2010bound, containing internal material and co\u2010existing with multiple ALP\u2010related vesicular compartments. Primary NMR skin fibroblasts display a similar vacuolation phenotype, indicating that this response is not an artefact of immortalisation or reporter expression. Together, these findings establish a live\u2010cell platform for analysing autophagy in NMR cells and identify a distinctive, reversible vacuolation response to lysosomal stress, consistent with dynamic remodelling of the lysosomal system within NMR skin fibroblasts.\n                  <\/jats:p>","DOI":"10.1111\/febs.70695","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:01:31Z","timestamp":1786705291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A live\u2010cell autophagy reporter reveals reversible vacuolation in naked mole\u2010rat skin fibroblasts under lysosomal stress"],"prefix":"10.1111","author":[{"given":"Fangze","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateo 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