FIGURE 2.

The ferroptosis process involves three key pathways: iron metabolism, amino acid metabolism, and lipid metabolism. Within the iron metabolism pathway, iron ions are taken up through the formation of a complex involving the transferrin receptor and transferrin, incorporating two iron molecules. Subsequently, these iron ions undergo endosomal uptake, where Fe ³⁺ is converted to Fe ²⁺ by STEP3 and then transported out by DMT1 from the exosome. Fe ²⁺ ions can either be stored in ferritin molecules or utilized for ferroptosis. NCOA4-mediated ferritinophagy enhances this process by degrading ferritin molecules, releasing sufficient iron for ferroptosis. In the amino acid metabolism pathway, the proper functioning of System Xc and GPX4 is crucial for preventing ferroptosis in cells. Meanwhile, the lipid metabolism pathways involve the ACSL/LPCAT/LOX axis, which provides lipid peroxides for ferroptosis induction. Conversely, pathways like NRF2 can prevent ferroptosis induction by transcriptionally activating the expression of SLC7A11 and GPX4, contributing to cellular homeostasis.