Fig. 1.

The process of ferroptosis. Ferroptosis is a form of nonapoptotic cell death characterized by overwhelming membrane lipid peroxidation and iron accumulation. Ferroptosis involves an imbalance in the oxidation and antioxidant systems. TFRC and LTF mainly promote ferroptosis by transferring Fe²⁺ into cells, while ferritin and SLC40A1 by storing iron and transporting iron out of cells, respectively. NCOA4-mediated ferritinophagy may play a role in regulating cellular iron levels by targeting ferritin for degradation. Subsequently, Fe²⁺ generates ROS through Fenton reaction. In particular, ACSL4, LPCAT3, SOAT1, TMEM164, ALOX, and POR pathways mediate the peroxidation of polyunsaturated fatty acids (PUFA), which is necessary for iron-mediated oxidative damage in ferroptosis. To counteract this oxidative stress, antioxidant defense systems have been identified, including SLC7A11-GSH-GPX4 and CoQ. Moreover, phospholipid modifying enzymes ACSL3 and MBOATs inhibit ferroptosis activity by promoting MUFA-PL synthesis. In the intricate network regulating lipid metabolism, ALDH1B1 and GSTP1 emerge as key players in ferroptosis. Their actions restrict the generation of 4-hydroxynonenal (4HNE), effectively acting as suppressors of ferroptosis.