{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:18:58Z","timestamp":1788427138122,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Smart Molecules"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cellular senescence involves progressive acidification, but how cells sense and adapt to this pH shift remains unclear. Here we report that metabolic enzyme GOT1 functions as a pH sensor that undergoes liquid\u2013liquid phase separation (LLPS) to combat senescence. Proteomic analysis identified GOT1 upregulation in aged human lung cells. Acidic conditions mimicking senescence directly induce GOT1 LLPS via its N\u2010terminal intrinsically disordered region (IDR1), recruiting ME1 to form dynamic enzymatic co\u2010condensates that scavenge reactive oxygen species and alleviate oxidative stress. To quantitatively interrogate GOT1's pH microenvironment during senescence, we engineered BDP\u2010PLP, a first\u2010in\u2010class fluorescent probe conjugating the native GOT1 cofactor pyridoxal phosphate to a BODIPY fluorophore. Operating via a binding\u2010inhibited PET mechanism, this probe enables high\u2010specificity GOT1 targeting and pH\u2010dependent fluorescence lifetime imaging (FLIM). Using FLIM, we achieved quantitative real\u2010time visualization of pH dynamics within GOT1 condensates in living cells, revealing that phase separation generates a highly acidic local microenvironment critical for its anti\u2010senescence function. This study uncovers a pH\u2010triggered phase separation mechanism that bolsters antioxidant defense via metabolic enzyme co\u2010condensation, offering new perspectives on metabolic adaptation in aging and establishing a chemical tool for probing microenvironmental dynamics.<\/jats:p>","DOI":"10.1002\/smo2.70096","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:57:41Z","timestamp":1788425861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A pH\u2010Responsive fluorescence lifetime probe reveals GOT1 phase separation in cellular anti\u2010senescence"],"prefix":"10.1002","author":[{"given":"Ziyue","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Technology Nanjing Normal University  Nanjing China"},{"name":"School of Food Science and Pharmaceutical Engineering Nanjing Normal University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology Nanjing Normal University  Nanjing China"},{"name":"School of Food Science and Pharmaceutical Engineering Nanjing Normal University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Bao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology Nanjing Normal University  Nanjing China"},{"name":"School of Food Science and Pharmaceutical Engineering Nanjing Normal University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Geriatrics Department of Geriatrics The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3894-4997","authenticated-orcid":false,"given":"Mingjiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Geriatrics Department of Geriatrics The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6462-095X","authenticated-orcid":false,"given":"Lina","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9526-7976","authenticated-orcid":false,"given":"Shuangshuang","family":"Wu","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Geriatrics Department of Geriatrics The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5399-8105","authenticated-orcid":false,"given":"Baoxing","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology Nanjing Normal University  Nanjing China"},{"name":"School of Food Science and Pharmaceutical Engineering Nanjing Normal University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/s43587-025-00910-5","volume":"5","author":"Majewska J.","year":"2025","journal-title":"Nat. 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