Ferroptosis in liver biology and diseases.

Abstract

Ferroptosis is a form of non-apoptotic cell death driven by iron-dependent lipid peroxidation (LPO). Ferroptosis is closely associated with hepatic metabolic pathways, particularly those involving iron, fatty acids, amino acids, and redox changes. This review aims to provide a comprehensive overview of the current molecular pathways and regulatory mechanisms underlying iron homeostasis and intracellular compartmentation in liver biology, emphasizing the roles of ferroptosis in several liver diseases, such as ischemia-reperfusion injury, drug-induced liver injury, viral hepatitis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, fibrosis, and hepatocellular carcinoma. We have also discussed the challenges of interpreting ferroptosis-related data, proposed a framework for defining ferroptosis, and highlighted future research directions as well as the therapeutic potential of targeting ferroptosis in the treatment of various liver diseases.