Fig. 6.

Chemical factors promote or inhibit pyroptosis. An example of a chemical factor that affects pyroptosis is α-KG, which is changed into L-2HG to trigger an increase in ROS levels as well as DR6 oxidation and polymerization to induce caspase-8 to cleave GSDMC and trigger pyroptosis. Drugs that enhance ROS production, or iron, result in Tom20 oligomerization and the formation of Bax pores, leading to cytochrome C release, which induces the cleavage of caspase-3/9 to trigger GSDME-dependent pyroptosis. Additionally, DMF interacts with GSDMD at the Cys191/Cys193 position to generate S-(2-succinyl)-cysteine, which prevents the combination of GSDMD and caspase. Galectin-1 induced by GSDMD can promote and enhance LPS-induced pyroptosis. Finally, Mg²⁺ blocks the influx of Ca²⁺ into the cells by restraining the ATP-gated calcium channel P2X7 to suppress GSDMD-NT oligomerization