{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:29:41Z","timestamp":1787135381022,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22277055"],"award-info":[{"award-number":["22277055"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22177100"],"award-info":[{"award-number":["22177100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Succinate dehydrogenase (SDH, complex II) connects the tricarboxylic acid (TCA) cycle to the electron transport chain (ETC), maintaining mitochondrial energy homeostasis. Selective SDH inhibition in diseased tissue has remained challenging due to the highly conserved catalytic architecture across normal tissues. Here, we reveal that SDH catalytic activity depends on the acetylation state of its catalytic subunit A (SDHA): the non\u2010acetylated form is catalytically active but exhibits fragile homeostasis in bladder cancer, contrasting with its robust maintenance in normal cells. Guided by this insight, we designed ZPI\u20103, a conformationally optimized inhibitor that selectively engages the non\u2010acetylated SDHA, suppressing tumor SDH activity and growth while sparing normal cells. In orthotopic NMIBC models, ZPI\u20103 outperforms mitomycin\u2010C. Differential SDH responses to ZPI\u20103 in clinical specimens further suggest its potential for patient stratification and precision therapy. These findings establish modification\u2010selective inhibition as a paradigm for tumor\u2010selective mitochondrial modulation.<\/jats:p>","DOI":"10.1002\/advs.77046","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:09:03Z","timestamp":1787134143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modification\u2010Selective Inhibition of Succinate Dehydrogenase a Enables Tumor\u2010Restricted Mitochondrial Modulation"],"prefix":"10.1002","author":[{"given":"Kaikai","family":"Xu","sequence":"first","affiliation":[{"name":"College of Chemistry and Materials Science Jiangsu Key Laboratory of Bio\u2010functional Materials Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials Nanjing Normal University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Kong","sequence":"additional","affiliation":[{"name":"College 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School Institute of Urology Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering Yancheng Institute of Technology  Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science Jiangsu Key Laboratory of Bio\u2010functional Materials Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials Nanjing Normal University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3836-3782","authenticated-orcid":false,"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science Jiangsu Key Laboratory of Bio\u2010functional Materials Jiangsu Collaborative Innovation Centre of 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