Modulation of Ferroptosis via the YY1-SLC7A11 Axis in Hepatic Ischemia-Reperfusion Injury Pathogenesis

• • YY1 overexpression significantly alleviates hepatic IRI in both in vitro and in vivo models, reducing infarct size and serum ALT/AST levels (p < 0.01), indicating its therapeutic potential for liver protection. • • NEDD4L-mediated K63-linked ubiquitination of YY1 at K339 leads to its proteasomal degradation, with NEDD4L upregulated during IRI, representing a specific molecular target for intervention. • • YY1 transcriptionally activates SLC7A11, a ferroptosis inhibitor; its suppression via YY1 degradation results in increased ferroptosis markers (e.g., lipid peroxidation, Fe2+ accumulation) and exacerbated liver damage. • • The NEDD4L-YY1-SLC7A11 axis is a critical pathway in hepatic IRI pathogenesis, offering a novel therapeutic strategy; however, clinical translation requires validation in human liver samples and further in vivo studies.