Table 1 Characteristics of the major types of cell death.
From: Diversity and complexity of cell death: a historical review
Classification | Type | Morphological features | Key regulator molecules | Major inhibitors (target) |
|---|---|---|---|---|
Non-RCD | Necrosis | Cell swelling, plasma membrane rupture, loss of organelle | - | - |
RCD-apoptotic | Apoptosis (Anoikis) | Cell shrinkage, nuclear condensation, apoptotic body fragmentation, nuclear membrane rupture, plasma membrane blebbing, loss of positional organization of organelles | Death receptors and their ligands, Bax, Bak, Bcl-2, AIF, caspase-3, caspase-8, caspase-9, TP53 | Z-VAD-FMK, emricasan, Q-VD-OPh, Z-VAD(OH)-FMK (pancaspase), Z-DEVD-FMK (caspase-3, -6, -7, and -10), Z-VDVAD-FMK (caspase-2), ivachtin (caspase-3), Ac-DEVD-CHO (caspase-3 and -7), Z-IETD-FMK (caspase-8), Q-LEHD-OPh (caspase-9) |
RCD-vacuole presenting | Autophagic cell death (Autosis) | Autophagic vacuolization, plasma membrane blebbing, organelle enlargement, depletion of cytoplasmic organelles | AMPK, mTOR, ULK1, PI3KIII, BECN1, ATGs, LC3, Na+/K+-ATPase | Chloroquine (lysosome), bafilomycin A1, concanamycin A (H+-ATPase), 3-methyladenine, wortmannin (PI3K), spautin 1(USP10 and USP13) |
|  | Entosis | Cell-in-cell structure | RhoA, ROCKI/II, E-cadherin, α-catenin, actomyosin, LC3, ATGs | C3-toxin (RhoA), Y-27632 (ROCK), blebbistatin (myosin) |
|  | Methuosis | Accumulation of large fluid‑filled single-membrane vacuoles, cell swelling, plasma membrane rupture | Ras, Rac1, Arf6, LAMP1, Rab7 | SP600125 (JNK) |
|  | Paraptosis | Accumulation of large fluid‑filled single-membrane vacuoles, dilation of the ER or mitochondria | mHCX, mNCX, MCU, VDAC, PyR, IP3R, SERCA, MAPKs | Actinomycin D, cycloheximide (ER stress) |
RCD-mitochondria dependent | Mitoptosis | Mitochondria disappearance, decomposition of the mitochondrial reticulum into small spherical organelles | Bax, Bak, TIMM8a (DPP), Drp1 | NAC, trolox (ROS) |
| Â | Parthanatos | Chromatic condensation, large DNA fragment formation, lack of apoptotic bodies and small-scale DNA fragments, loss of membrane integrity, lack of cell swelling | PARP, AIF | BYK204165, AG-14361, iniparib (PARP1) |
RCD-metal dependent | Ferroptosis | Small mitochondria, reduced number of mitochondrial cristae, elevated mitochondrial membrane density, increased rate of mitochondrial membrane rupture | System XC-, GPX4, lipid ROS | Deferoxamine, ciclopirox, deferiprone (Fe), ferrostatin-1, liproxstatin-1, β-mercaptoethanol, vitamin E, β-carotene, NAC, XJB-5-131, zileuton, CoQ10, baicalein (ROS), vildagliptin, alogliptin, linagliptin (DPP4), thiazolidinedione, rosiglitazone (ACSL4), selenium (GPX4) |
| Â | Cuproptosis | Mitochondrial shrinkage | SLC31A1, ATP7B, FDX1 | GSH (chelate Cu), UK5099 (MPC), rotenone, antimycin A (ETC) |
RCD-immunogenic | Necroptosis | Cell swelling, plasma membrane rupture, moderate chromatin condensation | Death receptors, TLRs, TCR, RIPKs, MLMK | Tetrahydroisoquinolines, lactoferrin, DNase (NETs), cl-amidine (PADI4) |
|  | Lysosomal cell death | Lysosomal and plasma membrane rupture | Cathepsins, STAT3, TP53, NF-κB, and MCOLN1 | CA-074Me (CTSB), deferoxamine (Fe), NAC (ROS) |
| Â | Pyroptosis | Lack of cell swelling, plasma membrane rupture, bubbling, moderate chromatin condensation and fragmentation | NLRs, ALRs, caspase-1, caspase-11, GSDMD | Disulfiram, LDC7559, Ac-FLTD-CMK, Polyphyllin VI (GSDMD), morroniside (MMP2/9) |
| Â | NETosis | Plasma membrane rupture, nuclear membrane collapse, chromatic fiber release | NOX4, PADI4 | Tetrahydroisoquinolines (NETs), cl-amidine (PADI4) |
Other | Alkaliptosis | Necroptosis-like morphology | NF-κB, IKBKB, CA9 | NAC, N-acetyl alanine acid (pH), IMD0354, CAY10657, SC514 (IKBKB) |
| Â | Oxeiptosis | Apoptosis-like morphology | KEAP1, PGAM5, AIFM1 | NAC (ROS) |
| Â | Erebosis | Loss of proteins, organelles, and nuclear contents; ACE accumulation; shortened microvilli; fragmented nuclei | Unknown | Unknown |
