Hippo pathway activation mediates cardiomyocyte ferroptosis to promote dilated cardiomyopathy through downregulating NFS1.

ABSTRACT: 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 ca

SUBMITTER: She G 

PROVIDER: S-EPMC11968290 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature