biostudies-literatureUnknown82She GCardiomyocyte loss by regulated death modes, like apoptosis and ferroptosis, has been implicated in the development of dilated cardiomyopathy (DCM). It remains unclear whether cardiomyocyte ferroptosis occurs as a consequence of Hippo pathway activation. Using a mouse model of DCM by overexpression of Mst1 transgene (Mst1-TG) leading to Hippo pathway activation, we showed that cardiomyocyte ferroptosis was evident by transcriptomic profiles, elevated mitochondrial Fe²⁺ content, increased levels of lipid peroxidation and obvious mitochondrial damage. Transcriptome revealed significant alterations of genes participating in iron metabolism and lipid peroxidation. Treatment of Mst1-TG mice with the ferroptosis inhibitor ferrostatin-1 reduced cardiomyocyte ferroptosis and improved caRedox biology103597https://www.ebi.ac.uk/biostudies/studies/S-EPMC11968290biostudies-literatureHippo pathway activation mediates cardiomyocyte ferroptosis to promote dilated cardiomyopathy through downregulating NFS1.PMC11968290Wu LHDeng XLSadoshima JZhang YJJia LYYang YYDu XJHai XXShe GPang ZDZhang YRen YJLai BCBai RYLi JJHan MZfalseHippo pathway activation mediates cardiomyocyte ferroptosis to promote dilated cardiomyopathy through downregulating NFS1.Cardiomyocyte loss by regulated death modes, like apoptosis and ferroptosis, has been implicated in the development of dilated cardiomyopathy (DCM). It remains unclear whether cardiomyocyte ferroptosis occurs as a consequence of Hippo pathway activation. Using a mouse model of DCM by overexpression of Mst1 transgene (Mst1-TG) leading to Hippo pathway activation, we showed that cardiomyocyte ferroptosis was evident by transcriptomic profiles, elevated mitochondrial Fe²⁺ content, increased levels of lipid peroxidation and obvious mitochondrial damage. Transcriptome revealed significant alterations of genes participating in iron metabolism and lipid peroxidation. Treatment of Mst1-TG mice with the ferroptosis inhibitor ferrostatin-1 reduced cardiomyocyte ferroptosis and improved ca2025-01-01T00:00:00Z2025 May2026-06-02T19:19:29.734Z2026-04-19T03:13:34.23ZS-EPMC119682904010701610.1016/j.redox.2025.103597