FIGURE 2.

Commonality of various PCDs among bacteria, animals, and plants. (A) Necroptosis is mediated by RIPK3-phosphorylated MLKL. The oligomerization of the 4-helice bundle in the N-terminal region of MLKL should form a cation channel in the plasma membrane and lead to disruption of membrane integrity. Inflammatory caspases were activated by canonical and/or non-canonical inflammosomes. The active inflammatory caspases can cleave gasdermins. The resulting N-gasdermins insert the plasma membrane and form a membrane pore with 18–21 nm in inner diameter. The gasdermin pore prefers the release of IL-1β and IL-18. Apoptosis is a non-lytic cell death. In the instinct pathway, the initiator caspase-9 is activated by the apoptosome consisting of apaf-1, Cyt c, and caspase-9; caspase-8 is activated by the death-inducing signaling complex (DISC) for extrinsic apoptosis. Caspase-8 is the molecular switch for apoptosis, for necroptosis, and pyroptosis. Ferroptosis is required for iron and is mediated by LOXs and ROS and POR and Cyt b. The lipid peroxides and lipid radicals are capable of being sequestered by GPX4 and FSP1, respectively. Upon infection, PANoptosis co-featured by pyroptosis, apoptosis, and necroptosis is present as well. (B) The bacterial gasdermins are conserved and commit cell death via pore-forming as well. cGAMP as the elicitor activates the phospholipase, which perturb membrane integrity and result in cell death. gRAMP, the giant repeat–associated mysterious protein from CRISPR-Cas type III effectors; TPR-CHAT, caspase HetF associated with the tetratricopeptide repeat. proteases (C) Resistance (R) protein-mediated HR and ferroptosis-like in the plant cell. The R protein ZAR1 (CC-NBS-LRR) with RKS1 and PBL2 ^UMP ligands form the pentameric complex. The funnel-like channel (∼0.5 nm in narrowest diameter) is a non-selective, Ca²⁺ influx, cation channel. Likewise, helper NLRs required for TLR (TIR-NB-LRR)-mediated HR constitute a Ca²⁺ influx, cation channel. But the definitive 3D models of helper NLRs remain elusive; other CNL resistosomes may be cation channels, but their 3D structures are not be determined. And, ferroptosis-like cell death was also observed in plant cells. (D) In total, GSDM and MLKL domains directly target the plasma membrane; the Bcl-2 family is responsible for mitochondrial membrane damages; and TIR-like sense and monitor energy deficit to produce a second messenger for downstream signaling.