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. 2022 Aug 5;9:966478. doi: 10.3389/fmolb.2022.966478

FIGURE 3.

FIGURE 3

p53 modulates GPX4-dependent ferroptosis pathways. p53 suppresses the transcription of SLC7A11, which is a core subunit of the System Xc−. SLC7A11 mediates cellular uptake of extracellular cystine in exchange for intracellular Glu, reduces downstream GSH and GPX4 biosynthesis, thus leading to ferroptosis. p53 also promotes ferroptosis through regulating other metabolic pathways. p53 can upregulate ALOX15 via SAT1-mediated, leads to lipid peroxidation and ferroptosis. p53 enhances the activity of SLC25A28, causes abnormal accumulation of redox-active iron and promotes ferroptosis. p53 also can suppress PHGDH and CBS respectively, limiting GSH production. p53 inhibits DPP4 by binding NOX1, boosting the production of ROS, and resulting in lipid peroxidation and ferroptosis. p21 is a target gene of p53. p21 suppresses GSH synthesis, and promotes ferroptosis.