Table 2.
Comparison between non-inflammatory cell death and proinflammatory cell death.
| Ferroptosis | Necroptosis | Pyroptosis | Apoptosis | Autophagic cell death | |
|---|---|---|---|---|---|
| Morphology | Increased plasma and mitochondrial membrane density, mitochondrial crest fracture, disappeared mitochondrial cristae | Organelle swelling, cell membrane rupture, degradation of cytoplasm and nucleus | Cell swelling, membrane blistering, DNA breakage, cell membrane rupture | Cell shrinkage, chromatin condensation, membrane blebbing, DNA fragmentation | Golgi and endoplasmic reticulum swelling, broken nucleus, the formation of a large number of phagocytic vesicles |
| Features | Intracellular iron overload, excessive lipid peroxidation | Necrosome complex formation, caspase-8 deficiency | Inflammasome formation, GSDMD pores on plasma membrane, IL-1β and IL-18 production and excretion | Apoptotic body formation, caspase family activation | Autophagic body formation, ATG proteins activation |
| Molecular biomarkers | HMOX1, PTGS2, GPX4, SLC7A11, Ferritin, FSP1, TFR1 | p-RIP1, p-RIP3, p-MLKL | NLRP3, GSDMD, Caspase-1, IL-1β | Caspase-3, BCL2, BAX, P53 | P62, LC3 II, ATG5, ATG7, Beclin-1 |
| Inducers | Erastin, RSL3, FIN56 | RIP1/RIP3/MLKL activator 1 | Lipopolysaccharide | Actinomycin, camptothecin, cyclotleximide | Brefeldin A, carbamazepine rapamycin |
| Inhibitors | Ferrostatin-1, liprostatin-1, deferoxamine | Necrostatin-1 | VX765, Z-VAD-FMK | Z-VAD-FMK | 3-Methyladenine, bafilomycin A1, hydroxychloroquine |
| Measurements | BODIPY 581/591 C11 assay, lipid peroxidation (MDA) assay, iron content assay, GSH and GSSG assay | Annexin V/PI assay, mitochondrial membrane potential assay | ELISA assay (IL-1β and IL-18), N-GSDMD and cleaved IL-1β content, caspase activation | Annexin V/PI assay, mitochondrial membrane potential assay, caspase activation | Autophagic flux assay, mCherry-eGFP-LC3 II fluorescence staining |
| Inflammation | Proinflammatory | Proinflammatory | Proinflammatory | Non-inflammatory | Non-inflammatory |
| major molecules related to inflammation | SLC7A11, GPX4, FSP1 | RIP1, RIP3, MLKL | NLRP3, Caspase-1, GSDMD | Caspase-3, Caspase-8, Caspase-9 | LC3 II, ATG5, ATG7 |
| Major inflammatory signaling pathways | JAK-STAT, NF-κB, inflammasome, cGAS-STING and MAPK signaling pathways | JAK-STAT, NF-κB, inflammasome, cGAS-STING and MAPK signaling pathways | JAK-STAT, NF-κB, inflammasome, cGAS-STING and MAPK signaling pathways | JAK-STAT, NF-κB, inflammasome, cGAS-STING and MAPK signaling pathways | JAK-STAT, NF-κB, inflammasome, cGAS-STING and MAPK signaling pathways |
GSDMD Gasdermin D, IL-1β Interleukin-1β, ATG Autophagy-related gene, HMOX1 Heme oxygenase 1, PTGS2 Prostaglandin endoperoxidase synthase 2, GPX4 Glutathione peroxidase 4, SLC7A11 Solute carrier family 7 member 11, FSP1 Ferroptosis suppressor protein 1, TFR1 Transferrin receptor 1, p-RIP1 Phosphorylated receptor interacting protein kinase 1, MLKL Mixed lineage kinase domain-like protein, NLRP3 NOD-like receptor family pyrin domain containing 3, BCL2 B-cell lymphoma 2, LC3 II Microtubule-associated protein 1 light chain 3 II, MDA Malonaldehyde, GSH Glutathione, GSSG Glutathione persulfide.