Fig. 1

Pathways controlling ferroptosis, necroptosis, and pyroptosis. Xc-complex imports cystine, which is used to synthesize glutathione. Glutathione is used by GPX4 to prevent lipid reactive oxygen species accumulation. In this context, the normal expression and function of Xc-complex and GPX4 are essential for the inhibition of ferroptosis under physiological conditions. Gasdermins form membrane pores to cause pyroptosis. The following three pathways have been confirmed to induce pyroptosis in mammals: (1) NLRP3/ASC/caspase-1/GSDMD axis, (2) caspase-4/5/11/GSDMD axis, and (3) caspase-3/GSDME axis. Membrane-associated MLKL induces necroptosis. When the function of caspase-8 is inhibited, the binding of TNF-α and its receptor could promote the assembly of a RIPK1-RIPK3-MLKL signaling complex. RIPK3-mediated phosphorylation of MLKL leads to MLKL translocation to the plasma membrane to trigger membrane damage. As a result of membrane damage, potassium ion outflow could further activate NLRP3 through NEK7, which may be a crosstalk with pyroptosis pathway