Skip to main content

Table 1 Comparison of different forms of cell death and their biological characteristics

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

  1. DAMP danger-associated molecular pattern, PAMP pathogen-associated molecular pattern, dsDNA double-stranded DNA, LPS lipopolysaccharide, NLRP NOD-like receptor protein, AIM2 absent in melanoma 2, TAK1 TGF-β-activated kinase-1, Gzm granzyme, TNF tumor necrosis factor, TRAIL-R TNF-related apoptosis-inducing ligand receptor, TLR Toll-like receptor, ZBP1 Z-DNA binding protein 1, RIPK receptor interacting serine/threonine kinase, TRADD tumor necrosis factor receptor type 1-associated death domain protein, MLKL mixed lineage kinase domain-like, GPX glutathione peroxidase, GSH glutathione, GPCR G-protein-coupled receptors, PAD peptidyl arginine deiminase, MPO myeloperoxidase, NE neutrophil elastase, NET neutrophil extracellular trap, GSDMD gasdermin D, mTOR mammalian target of rapamycin, ULK Unc-51-like kinase, PtdIns3K class III phosphatidylinositol 3-kinase, WIPI WD repeat domain phosphoinositide-interacting protein