Table 1 Comparison of select cell death forms

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 X_C⁻, 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

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