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Elevated oxidative phosphorylation (OXPHOS) has been linked to cancer stemness, a determinant of chemoresistance. However, the mechanisms underlying increased OXPHOS during cancer cell chemoresistance remain unclear. This study revealed that the mitochondrial translational activator of cytochrome oxidase subunit 1 (TACO1) is linked to stemness and cisplatin resistance in BCa cells. Mechanistically, mitochondrial TACO1 enhances the translation of the mitochondrial cytochrome c oxidase I (MTCO1), promoting mitochondrial reactive oxygen species (mtROS) by upregulating OXPHOS, consequently driving cancer stemness and cisplatin resistance. Intriguingly, the mitochondrial translocation of TACO1 is mediated by the heat shock protein 90 \u03b2 (HSP90\u03b2), a process that requires circFOXK2 as a scaffold for the TACO1\u2010HSP90\u03b2 interaction. The mutations at the binding sites of TACO1\u2010circFOXK2\u2010HSP90\u03b2 disturb the ternary complex and inhibit cancer stemness and cisplatin resistance in BCa cells by suppressing the MTCO1\/OXPHOS\/mtROS axis. Clinically, BCa patients with increased mitochondrial TACO1 expression respond poorly to cisplatin treatment. This study elucidates the mechanisms by which TACO1 promotes BCa stemness and cisplatin resistance, providing a potential target for mitigating cisplatin resistance for BCa and a biomarker for predicting cisplatin response.<\/jats:p>","DOI":"10.1002\/advs.202408599","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T14:35:31Z","timestamp":1733841331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer"],"prefix":"10.1002","volume":"12","author":[{"given":"Minhua","family":"Deng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou 510060 China"},{"name":"Department of Urology Sun Yat\u2010Sen 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