Figure 4.

Lipid mechanism in pyroptosis. Pyroptosis is a proinflammatory form of programmed cell death characterized by the formation of membrane pores. The process of pore formation is executed through the inflammasome-mediated cleavage and activation of GSDMD. Lipids, including oxysterols, fatty acids, and phospholipids, play complex and critical roles in pyroptosis. For instance, the activation of the NLRP3 inflammasome requires binding to cholesterol in the endoplasmic reticulum, while the stable oligomerization of NLRP3 is facilitated by phosphoinositides (PIPs), and cardiolipin promotes NLRP3 inflammasome formation. Moreover, the functionality of GSDMD pores is dependent on phosphoinositides, and the enrichment of phosphatidylinositol-4,5-bisphosphate (PtdIns [4,5]P₂) directly enhances their dynamics.