Integrated hepatic ferroptosis gene signature dictates pathogenic features of ferroptosis

Ferroptosis is a unique form of cell death induced by iron-dependent lipid peroxidation, implicated in various biological contexts including liver disease. Establishing an iron overload-induced ferroptosis model and identifying hepatic gene signatures associated with ferroptosis are crucial for understanding its role in liver pathogenesis. F-box and leucine-rich repeat protein 5 (FBXL5) is a substrate recognition component of the SCF E3 ligase complex that restricts intracellular iron levels. The present study employed liver-specific FBXL5-null mice to establish an iron overload-induced ferroptosis model. Transcriptome analysis revealed a set of genes associated with hepatic ferroptosis response, facilitating the understanding of ferroptosis-related pathology in liver injury models. The present study establishes a murine model of iron overload-induced hepatic ferroptosis and identifies a gene signature indicative of hepatic ferroptosis response both in mice and humans.