{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:47:02Z","timestamp":1791809222397,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sirtuin\u20101 (SIRT1) is an NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u2010dependent deacetylase implicated in autophagosome formation; however, whether SIRT1 also regulates autophagosome clearance during late\u2010stage autophagy remains unclear. Here, we investigated the role of SIRT1 in autophagosome clearance during autophagy and mitophagy in cardiomyocytes. Mitochondrial stress induced by carbonyl cyanide m\u2010chlorophenyl hydrazone (CCCP) decreased mitochondrial protein levels and increased phosphorylation of ubiquitin, a PINK1 target, in H9c2 cardiomyocytes. These CCCP\u2010induced decreases in mitochondrial proteins were prevented by co\u2010treatment with chloroquine, an inhibitor of lysosomal degradation, supporting the induction of CCCP\u2010triggered mitophagy. SIRT1 knockdown similarly prevented the CCCP\u2010induced reduction in mitochondrial proteins and led to the accumulation of autophagosomes containing fragmented mitochondria without attenuating ubiquitin phosphorylation, suggesting that SIRT1 acts downstream of mitochondrial tagging. Tandem GFP\u2013RFP LC3 assay and LC3\u2013LAMP1 colocalization analysis demonstrated impaired autophagosome\u2013lysosome fusion following SIRT1 knockdown. In\u00a0vivo, cardiomyocyte\u2010specific SIRT1 knockout mice exhibited elevated basal LC3\u2010II levels and a blunted LC3\u2010II response to chloroquine, consistent with impaired autophagic flux. In a doxorubicin (DOX)\u2010treated model, SIRT1 deficiency attenuated autophagosome degradation during the early period after DOX administration. Mechanistically, SIRT1 interacted with Rab7, a key regulator of autophagosome\u2013lysosome fusion, raising the possibility that SIRT1 might regulate fusion through post\u2010translational modification of Rab7 or related components. Collectively, these findings identify SIRT1 as a regulator of autophagosome\u2013lysosome fusion that promotes autophagosome degradation during autophagy and mitophagy in cardiomyocytes.\n                  <\/jats:p>","DOI":"10.1096\/fj.202601047r","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:20:57Z","timestamp":1791292857000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SIRT1 Regulates Late Stage of Autophagy and Mitophagy via Autophagosome\u2013Lysosome Fusion in Cardiomyocytes"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-1297","authenticated-orcid":false,"given":"Atsushi","family":"Kuno","sequence":"first","affiliation":[{"name":"Department of Pharmacology Sapporo Medical University School of Medicine  Sapporo Hokkaido Japan"},{"name":"Division of Cardiovascular\u2010Kidney\u2010Metabolic Medicine, Department of 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