Mechanisms and active substances of targeting lipid peroxidation in ferroptosis regulation

Abstract

Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases, such as liver disease, acute kidney injury, cardiovascular disease, neurodegenerative disease and cancer. Lipid-based reactive oxygen species (ROS), particularly lipid hydroperoxides in the cellular membrane can lead to membrane disruption and cell death mediated by ferroptosis. There are three necessary stages involving in the process of lipid peroxidation regulation in ferroptosis, including the synthesis of membrane phospholipids, initiation of lipid peroxidation and clearance of lipid peroxides. In this review, we summarized the molecular modulation mechanisms of lipid peroxidation in ferroptosis from the above three stages, as well as various ferroptosis modulators targeting lipid peroxidation, including commonly used products, natural bioactive compounds and selenocompounds. Collectively, these findings suggest the vital role of lipid peroxidation in ferroptosis, and targeting lipid peroxidation in ferroptosis is potential to treat ferroptosis-associated diseases.