Modulation of ferroptosis via YY1-SLC7A11 axis in hepatic ischemia-reperfusion injury pathogenesis

• YY1 is downregulated during hepatic ischemia-reperfusion injury (IRI), and its overexpression alleviates liver damage both in vitro and in vivo. • The E3 ligase NEDD4L promotes K63-linked ubiquitination of YY1 at K339, leading to proteasomal degradation and exacerbation of IRI. • YY1 transcriptionally upregulates SLC7A11, a ferroptosis inhibitor, thereby suppressing ferroptosis and reducing liver injury. • Targeting the NEDD4L-YY1-SLC7A11 axis offers a novel therapeutic strategy for hepatic IRI.