TABLE 1.
The main features of ferroptosis, apoptosis, autophagy, necroptosis, and pyroptosis.
| Ferroptosis | Apoptosis | Autophagy | Necroptosis | Pyroptosis | ||
| Morphological features | Cell morphology | Smaller and rounder; cell rounding up | Shrinkage; intercellular connections disappear |
Minor changes | Swelling | Swelling; formed bubble-like protrusions |
| Cell membrane | No rupture or blistering | Plasma membrane blebbing; membrane structure remains intact | Blebbing sometimes observed | Rupture of plasma membrane | Formation of plasma membrane pores; plasma membrane rupture |
|
| Cytoplasm | Small mitochondria with condensed mitochondrial membrane densities | Retraction of pseudopods; dense cellular contents |
Vacuolization of the cytoplasm; accumulation of double-membraned autophagic vacuoles |
Cytoplasmic swelling, swelling of cytoplasmic organelles | Osmotic swelling; cell contents leakage | |
| Nucleus | Normal nuclear size; lack of chromatin condensation |
Genetic materials fragmentation; marked chromatin condensation; nuclear fragmentation and condensation |
Lack of chromatin condensation | Mild-moderate chromatin condensation (Nuclear pyknosis) | Chromatin random breakage degradation | |
| Special features | Mitochondrial atrophy or fragmentation; mitochondrial membrane density condensed; mitochondrial cristae decreased |
Apoptotic bodies (or ApoBDs) | Numerous autophagosomes and autolysosomes | Necroptotic bodies | Pyroptotic bodies | |
| Biological features | Iron and ROS accumulation; lipid peroxides increased; system Xc– and GPX4 inhibition; GSH depletion; Δψm dissipation |
Caspase activation; DNA fragmentation; Δψm dissipation; intracellular calcium increased |
LC3-I to LC3-II conversion; ATG expression increased; increased lysosomal activity |
Activation of RIP1, RIP3, and MLKL; PARP1 hyperactivation; drop in ATP levels |
Dependent on caspase-1; GSDMD family activation |
|
| Immunological features | Release of DAMPs (e.g., inflammatory factor, arachidonic acid mediators, HMGB1) |
Release Ecto-CRT, Histone, HMGB1, and ATP under certain conditions | Regulation of immune cell differentiation and function | Release of DAMPs (e.g., DNA, IL-6 and HMGB1) | Release of proinflammatory cytokine | |
| Inflammation | Pro-inflammatory | Anti-inflammatory | Mostly anti-inflammatory | Mostly pro-inflammatory | Pro-inflammatory | |
| Major regulatory components | P53, HO-1, iron, systemXC-/GSH/GPX4 pathway, GCH1/DHFR/BH4 pathway, FSP1/CoQ10 pathway, DHODH/CoQ pathway, p62/Keap1/Nrf2 pathway |
P53, Bax and other Bcl-2 family proteins, Caspase family, endoplasmic reticulum pathway, death receptor |
ATG family proteins (e.g., Atg5 and Atg7), Beclin 1, PI3K-AKT-mTOR pathway, MAPK-ERK1/2-mTOR pathway |
Toll-like receptor family, RIP1, RIP3, MLKL, TNF-α, TRAIL, FasL, ROS |
Caspase-1, Caspase-4/5/11, GSDMD, IL-1β, IL-18, NLRP3-mediated signaling pathway |
|
| Main inducer and inhibitor |
Inducer | Erastin, sulfasalazine, sorafenib, altretamine, RSL3, ML162, ML210, SAS, lanperisone, DPI7, DPI10, FIN56, CIL56, artemisinin, FINO2 | Ca2+/Mg2+, TGF-β glucocorticoid, FASL |
Rapamycin, lithium, sodium, brefeldin A, thapsigargin, tunicamycin valproate, carbamazepine, xestospongin B/C, C2-ceramide |
Sorafenib, artesunate, shikonin, resibufogenin, 5-FU, SM-164 | Paclitaxel, VTPA, ZnO-NPs, ivermectin |
| Inhibitor | Deferoxamine, deferiprone, vitamin E, ferrostatin-1, Liproxstatin-1, DHO, SRS, CA-1, cycloheximide |
IAPs (XIAP, c-IAP1/2, ILP-2, NAIP, ML-IAP/livin, Z-VAD-FMK etc.), IL-2/3/4, GM/CSF |
SAR405, Bafilomycin A1, Wortmannin, LY294002, Spautin1, 3-Methyladenine, hydroxychloroquine |
Necrostatin-1, Necrostatin-2, NSA, Kongensin- A |
Necrosulfonamide, VX765, Z-VAD-FMK, Q-VD-Oph |
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