From: Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases
Pyroptosis | Apoptosis | Necroptosis | Ferroptosis | NETosis | Autophagy | |
---|---|---|---|---|---|---|
Death stimulus | DAMPs and PAMPs, dsDNA, pathogens, LPS, anthrax lethal toxin, microbial toxins and metabolites, viral RNA, extracellular ATP, lysosomal damage, permeabilization of the cell membrane to potassium ions, etc. | DNA damage, hypoxia, viral infection, toxins | Ischemia–reperfusion, physical or chemical trauma, viral or bacterial infection, etc. | Decreased cysteine (e.g., erasin) or glutamine uptake, increased iron uptake (extrinsic), inhibition of GPX4 (e.g., RSL3) (intrinsic) | Bacterial components, fungal β-glucan, cytokines | mTOR inhibitor, trehalose, treatment with etoposide, staurosporine, thapsigargin |
Initiator | Activation of inflammasomes (e.g., NLRP3, NLRC4, AIM2, pyrin, etc.)/DR binding to TAK1/activation of GzmA or GzmB/neutrophil elastase/cathepsin G | Death receptor (TNF superfamily) activation (extrinsic)/ intracellular signals (intrinsic) | Death receptor activation (TNFR1, CD95, TRAIL-R1, TRAIL-R2, TLR3, TLR4, ZBP1) dependent on caspase-8 inhibition | System \(\chi_{{\text{c}}}^{ - }\) inhibition, depletion of GSH | Activation of neutrophil surface receptors, such as GPCRs, TNF, and Fc receptors (neutrophil activation) | ULK complex (consisting of ATG101, ATG13, FIP200) and ATG9 |
Regulator/mediator | Nek7 | Caspase-8 (extrinsic)/caspase-9 (intrinsic) | RIPK1‐RIPK3 | Inhibition of GPX4, iron metabolism-related proteins | Combined action of PAD4, NE, and MPO, serine proteases | PtdIns3K complexes, ATG2-Atg18/WIPI complexes, the ATG12 conjugation system, the Atg8/microtubule-associated protein 1 light chain 3 (LC3) conjugation system |
Executor | Caspase‐1, caspase‐4/5/11, caspase-3/8, gasdermin family | Caspase‐3, 7 | MLKL oligomerization, translocation to the inner leaflet of the plasma membrane | Iron-dependent lipid peroxidation | Dysregulated NETs, GSDMD | Autophagosome, autolysosome |
Morphology | ||||||
Plasma membrane rupture | Yes | No (membrane blebbing) | Yes | Yes | Yes | No |
Cell swelling | Yes | No (cell shrinkage) | Yes | No (rounding up) | Yes | No |
Nuclear membrane integrity | Yes | No | No | No | No | – |
DNA fragmentation | Yes | Yes | Yes | No | No | – |
Chromatin condensation | Yes | Yes | Yes | No | No | – |
Mitochondria damage | Yes (swelling) | Yes (swelling?/condensation?) | Yes (ruptured mitochondrial outer membrane, decreased or vanished mitochondria cristae, condensed mitochondrial membrane) | Yes (membrane densities, reduction or vanishing of mitochondria crista, outer mitochondrial membrane rupture) | Yes (swelling) | Yes |
Lytic cell death | Yes | No | Yes | Yes | Yes | – |
Inflammation | Yes | No | Yes | Yes | Yes | Partially have |