ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis

Reactive oxygen species (ROS) mediate lipid peroxidation and produce 4-hydroxynonenal and other related products, which play an important role in the process of cell death, including apoptosis, autophagy, and ferroptosis. Lipid peroxidation of phospholipid bilayers can promote mitochondrial apoptosis, endoplasmic reticulum stress, and other complex molecular signaling pathways to regulate apoptosis. Lipid peroxidation and its products also act at different stages of autophagy, affecting the formation of autophagosomes and the recruitment of downstream proteins. In addition, we discuss the important role of ROS and lipid peroxides in ferroptosis and the regulatory role of nuclear factor erythroid 2-related factor 2 in ferroptosis under a background of oxidation. Finally, from the perspectives of promotion, inhibition, transformation, and common upstream molecules, we summarized the crosstalk among apoptosis, autophagy, and ferroptosis in the context of ROS. Our review discusses the role of ROS and lipid peroxidation in apoptosis, autophagy, and ferroptosis and their possible crosstalk mechanisms, so as to provide new insights and directions for the study of diseases related to pathological cell death. This review also has referential significance for studying the exact mechanism of ferroptosis mediated by lipid peroxidation.

Automated summary

Reactive oxygen species (ROS) play a crucial role in cell death processes such as apoptosis, autophagy, and ferroptosis through lipid peroxidation. The oxidation of phospholipid bilayers can trigger mitochondrial apoptosis and endoplasmic reticulum stress, while also affecting autophagy. Additionally, ROS and lipid peroxides are involved in ferroptosis, and the nuclear factor erythroid 2-related factor 2 regulates ferroptosis under oxidative conditions. This review provides insights into the interplay among apoptosis, autophagy, and ferroptosis mediated by ROS and lipid peroxidation, offering new directions for studying diseases related to pathological cell death.