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DEAD\u2010box helicase 17 (Ddx17), a member of the DEAD\u2010box RNA helicase family, is known to regulate mitochondrial function, but its role in SICM remains unclear. In this study, mice with cardiomyocyte\u2010specific Ddx17 knockdown (Ddx17\u2010cKD) and overexpression (Ddx17\u2010OE) were generated, and sepsis models were established using cecal ligation and puncture. Mechanistic findings were further validated in\u00a0vitro using immunoprecipitation and dual\u2010luciferase assays. Ddx17 expression was markedly reduced in the cardiac tissues of septic mice and in lipopolysaccharide\u2010treated cardiomyocytes. Knockdown of Ddx17 increased mitochondrial reactive oxygen species accumulation, enhanced cell death and decreased superoxide dismutase activity. In contrast, Ddx17 overexpression attenuated mitochondrial apoptosis and oxidative stress, restored adenosine triphosphate production and mitochondrial membrane potential and improved cardiac function in septic mice. Mechanistically, Ddx17 interacted with signal transducer and activator of transcription 3 (STAT3) to suppress transcription of the mitochondrial fission protein dynamin\u2010related protein 1 while maintaining the level of the fusion protein mitofusin 1, thereby preserving mitochondrial integrity and cardiomyocyte homeostasis. These findings demonstrate that Ddx17 protects against sepsis\u2010induced cardiomyopathy by regulating mitochondrial dynamics, reducing oxidative stress and preventing apoptosis, thereby highlighting Ddx17 as a potential therapeutic target for septic cardiac dysfunction.<\/jats:p>","DOI":"10.1111\/1440-1681.70105","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T04:04:43Z","timestamp":1770609883000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ddx17 Mitigates Sepsis\u2010Induced Cardiomyopathy by Regulating Mitochondrial Dynamics in Cardiomyocytes"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9331-6594","authenticated-orcid":false,"given":"Ya\u2010ting","family":"Jiang","sequence":"first","affiliation":[{"name":"Emergency Department Ningbo No. 2 Hospital  Ningbo 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