Table 1 A comparison of features associated with various types of programmed cell death [16, 121,122,123,124,125].
From: Ferroptosis, pyroptosis and necroptosis in acute respiratory distress syndrome
Type | Morphological features | Biochemical features | Immune features | Positive regulators | Negative regulators |
|---|---|---|---|---|---|
Ferroptosis | Cell membrane: plasma membrane blebbing and lacking rupture Cytoplasm: shrunken mitochondria, increased mitochondrial membrane density, disruption of membrane integrity. Nucleus: lack of chromatin condensation and margination. | Iron and ROS accumulation. Formation of lipid peroxidation products (e.g., MDA and 4-HNE). GSH depletion. NADPH oxidases (NOXs) are activated and released by the arachidonic acid mediators. | Proinflammatory due to the release of DAMPs. Activation of NF-κB and MAPK pathways | VDAC2/3 NCOA4 NOXs ALOXs P53 TFR1 FTH1 ACSL4 PTGS2 | GPX4 SLC7A11 GSH NRF2 HSPB1 |
Pyroptosis | Cell membrane: cell swelling and plasma membrane blebbing. Cytoplasm: formation of vesicles and inflammasomes. Nucleus: chromatin condensation and nuclear fragmentation. | Activation of caspases 1/4/5/11 and GSDMD cleavage. Releasing IL-1β and IL-18. | Robust proinflammatory due to release inflammatory factors and DAMPs. | Caspases 1/3/4/5/8 PRKN GSDMD IRGB10 TLR7 | |
Necroptosis | Cell membrane: cell shrinkage and plasma membrane blebbing. Cytoplasm: cytoplasmic and cytoplasmic organelles swelling. Nucleus: moderate chromatin condensation. | Activation of RIPK1, RIPK3, and MLKL and formation of necrosome. Drop in ATP. Releasing DAMPs. | Most often proinflammtory due to the release DAMPs. In some cases anti-inflammatory | RIPK1, RIPK3 MLKL TNFR1 | STUB1 A20 AURKA Protein phosphatase |
Apoptosis | Cell membrane: plasma membrane blebbing and cell shrinkage. Cytoplasm: cleavage of cytoskeletal proteins and collapse of subcellular components. Nucleus: chromatin condensation and nuclear fragmentation. | Caspases activation and cleave numerous proteins. Fragmentation of DNA. | Often anti-inflammatory and immune silent. In some cases proinflammatory | P53 Caspases Bax Bak Fas FasL | Bcl-2 Bcl-XL |
Autophagy | Cell membrane: lack of change and may exist the plasma membrane blebbing. Cytoplasm: swelling of cytoplasmic organelles and formation of autophagosomes. Nucleus: nuclear fragmentation and lack of chromatin condensation. | LC3-I to LC3-II conversion Substrate (e.g., p62) degradation. | Most often anti-inflammatory due to inhibit the inflammasome activation. Proinflammatory due to mediation of secretion of cytokines. | ATG5 ATG7 ATG3 Utx Beclin 1 Rala |
