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. Author manuscript; available in PMC: 2023 Jul 1.
Published in final edited form as: Prog Lipid Res. 2022 Jul 25;87:101182. doi: 10.1016/j.plipres.2022.101182

Figure 1.

Figure 1

Schematic representation of lipids involved in the canonical and non-canonical NLRP3 activation pathways. In the canonical activation, NLRP3 activation is caused by the K+ efflux that can be induced by cholesterol crystals, sphingosine and saturated fatty acids (SFAs) such as palmitic and stearic acids and can be inhibited by unsaturated fatty acids (UFAs). Interaction with cholesterol and negatively charged lipids such as cardiolipin, and phosphatidylinositols in organelles membranes favors NLRP3 activation and interaction with ASC and caspase-1. Active caspase-1 cleaves gasdermin D (GSDMD), pro-IL18, and pro-IL1β causing pore membrane formation and cytokine release. In the non-canonical pathway, bacterial lipopolysaccharides (LPS), lipophosphoglycans (LPG) or ornithine lipids (OL) or host-derived oxidized phospholipids (oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine, oxPAPC) activate caspase-11, which cleaves GSDMD, inducing membrane pore formation. The consequent K+ efflux activates in turn the NLRP3 inflammasome. Both canonical and non-canonical pathways culminate in Ninjury-1-mediated lytic cell death. The NLRP3 inflammasome could be also activated by cationic lipids through an unknown mechanism.