Table 1.
Comparison of select cell death forms
| Inducers | Key constituents | Characteristics | Cell release | Immune features | |
|---|---|---|---|---|---|
| Apoptosis (PCD) | TNF-α, FasL, TRAIL, Hypoxia, Irradiation, Heat shock | Bcl-2 protein family, P53, Caspase-2/3/6/7/8/9/10, HSPs | Plasma membrane blebbing, Reduced cellular volume, Nuclear fragmentation and chromatin condensation |
In certain cases: DAMPs (e.g., dsDNA, HMGB1, ATP, calreticulin) |
Mostly anti-inflammatory. Pro-inflammatory in cases involving the release of DAMPs |
| Pyroptosis (PCD) | DAMPs, PAMPs, Microbial infection | GSDM protein family, Caspase-1/3/4/5/8/11, Inflammasomes | Plasma membrane rupture and pore formation, Cytoplasmic swelling, Chromatin condensation | Intracellular content, DAMPs (e.g., IL-18, IL-1β, dsDNA, ATP, HMGB1) | Pro-inflammatory |
| Necroptosis (PCD) | TNF-α, TRAIL, Fas ligand, Microbial infection | MLKL, RIPK1/3 (Necrosome), TRADD | Plasma membrane rupture, Cytoplasmic and organelle swelling, Moderate chromatin condensation | Intracellular content, DAMPs (e.g., IL-1α, IL-33, IL-6, HSPs) | Mostly pro-inflammatory. Anti-inflammatory in certain cases |
| Ferroptosis (PCD) | ROS from iron accumulation and lipid peroxidation | GPX4, System XC−, GSH, ACSL4 | No plasma membrane blebbing or rupture, Small mitochondria with ruptured outer membrane, Normal nucleus | DAMPs (e.g., HMGB1, dsDNA), lipid oxidization products (e.g., 4-HNE, LTB4) | Pro-inflammatory |
| Necrosis (Accidental) | Microbial infection, Toxins, Trauma, Ischemia, Thermal stress | Unspecific | Plasma membrane rupture, Cytoplasmic and organelle swelling, Random DNA degradation | Intracellular content, DAMPs (e.g., IL-1α, IL-33, dsDNA, ATP, HMGB1) | Pro-inflammatory |
ACSL4, Acyl-CoA synthetase long-chain family member 4; Bcl-2, B-cell lymphoma 2; DAMPs, danger-associated molecular patterns; dsDNA, double-stranded DNA; GPX4, glutathione peroxidase 4; GSDM, gasdermin; GSH, glutathione; HMGB1, high-mobility group box protein 1; HSPs, heat shock proteins; IL, interleukin; LTB4, Leukotriene B4; MLKL, mixed lineage kinase domain-like protein; PAMPs, pathogen-associated molecular patterns; PCD, programmed cell death; RIPK1/3, receptor-interacting serine/threonine-protein kinase 1/3; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-alpha; TRADD, TNFR-associated death protein; TRAIL, TNF-related apoptosis-inducing ligand; XC−, cysteine/glutamate transporter receptor; 4-HNE, 4-Hydroxynonenal