Fig. 4

The crosstalk between ferroptosis and apoptosis, necroptosis, autophagy-dependent cell death and pyroptosis. a.The crosstalk between ferroptosis and apoptosis. Starvation and treatment of gallic acid and irradiation lead to upregulated ROS, and ROS in turn induces apoptosis and ferroptosis (via lipid ROS). ROS is decreased by TRIP-Br1, which is inhibited by the PI3K/Akt pathway. PUFAs induce ferroptosis in the form of lipid ROS, as well as apoptosis via the PPARγ/SDC-1 pathway. The lipid ROS is reduced by GPX4 and GSH, which are inhibited by DT in danshen and PEITC, respectively. DT and PEITC also induce apoptosis. P53 induces ferroptosis by inhibiting SLC7A11 and apoptosis by regulating genes such as BAX, APAF-1, PUMA, p53AIP1, PIDD and NOXA. b. Cystine starvation induces a decrease in GSH and subsequent increase in intracellular ROS, which triggers ferroptosis. The increased ROS also induces necroptosis via the RIPK1/RIPK3/MLKL pathway. TRIP-Br1 suppresses ferroptosis and necroptosis by inhibiting ROS production. In addition, MLKL upregulates CHAC1 via the GCN2/eIF2α/ATF4 pathway, and CHAC1 decreases the level of GSH. Upregulated RIPK3 causes breast cancer cells to rely on cystine and undergo necroptosis and ferroptosis upon cystine deprivation. c. Siramesine and lapatinib induce both ferroptosis and autophagy by upregulating cellular ROS. d DHA triggers both ferroptosis and pyroptosis in breast cancer cells.