Table 1 The main morphological features, regulators, inducers and inhibitors of ferroptosis, apoptosis, necroptosis, autophagy-dependent cell death and pyroptosis

Ferroptosis

Mitochondria become smaller, with increased mitochondrial membrane densities and reduced mitochondrial crista, outer mitochondrial membrane rupture and normal nucleus [4]

Iron accumulation; lipid peroxidation; ΔΨm elevated; caspase-independent [22]

GPX4 [23], p53 [24,25,26], HSPB1 [27, 28], SLC7A1 1[4], NRF2 [29,30,31], TFRC [14, 32], NCOA4 [16, 33], ACSL4 [17, 34,35,36], FSP1 [37]

GPX4 inactivation due to GSH depletion (class I FINs): erastin [4, 13], erastin derivatives (piperazine erastin [23], imidazole ketone erastin [15]), DPI2 [23], buthionine sulfoximine [23], sulfasalazine [4, 38], sorafenib [39], glutamate [4], cyst(e) inase [40], BAY 87–2243 [41, 42];

GPX4 inactivation/depletion (class II, III FINs): 1S,3R-RSL3 [4, 14, 23], DPI7/ML162, DPI10/ML210, DPI12, DPI13, DPI17, DPI18, DPI19 [23, 43], altretamine [44], FIN56 [45, 46], withaferin A [47], fluvastatin, lovastatin acid, simvastatin [48];

Iron loading (class IV FINs): hemoglobin [49], FeCl₂ [49], hemin [47], (NH₄)2Fe(SO₄)₂ [47], non-thermal plasma [50], salinomycin [51], amino acid depletion +Cornell dots [52], lapatinib + siramesine [12], FINO₂ [45], BAY 11–7085 [53];

others: lanperisone [54], artemisinin derivatives [55, 56], CIL41, CIL56, CIL69, CIL70, CIL75, and CIL79 [46]

Iron chelators: desferoxamine [4], solamine [4], 2, 2- Bipyridyl [4];

Anti-oxidants: vitamin E [23], U0126 [4, 23], Trolox [4];

ROS formation inhibitors: ferrostatin-1 [4], SRS8–72 [4], SRS11–92, SRS12–45,SRS13–35, SRS13–37 [57], SRS16–86 [58];

Others: cycloheximide [4], aminooxyacetic acid [4], ebselen [4, 59], β-mercaptoethanol [4, 60]

Apoptosis

Plasma membrane blebbing; cellular and nuclear volume reduction; chromatin agglutination, nuclearfragmentation;

formation of apoptotic bodies and cytoskeletal disintegration, no significant changes in mitochondrial structure [61]

Activation of caspases; DNA fragmentation; ΔΨm dissipation; phosphatidylserine exposure [22]

CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CASP10, CARD8, GZMB, HSPA1B, CARD6, NOX5, p53, Bax, Bak, BCL2 family (e.g., BAK1, BAX, BOK, BCL2L11, BBC3, PMAIP1, BID, BCL2, BCL2L1, MCL1, BCL2L2, and BCL2L10), Bcl-XL [19, 62]

Extrinsic apoptosis: FASL, DCC,

Intrinsic apoptosis: multiple intracellular stress conditions

(e.g. DNA damage, cytosolic Ca²⁺ overload) [61]

Inhibitors of apoptosis (IAPs): XIAP, c-IAP1, c-IAP2, ILP-2, ML-IAP/livin, NAIP, Bruce/Apollon, survivin [63];

caspase inhibitors: Z-VAD-FMK, emricasan, Q-VD-OPh, Z-VAD (OH)- FMK, Z-DEVD-FMK, Z-VDVAD-, ivachtin, Q-DEVD-OPh, Ac-DEVD-CHO, Z- IETD-FMK, Q-LEHD-OPh [22]

Necroptosis

Plasma membrane breakdown, generalized swelling of the cytoplasm and organelles, moderate chromatin condensation [61]

Drop in ATP levels; activation of RIPK1, RIPK3, and MLKL; cytosolic necrosome formation [5, 22]

RIP1, RIP3, MLKL, ESCRT-III, cIAPs, LUBAC, PPM1B, and AURKA [19, 22, 64]

TNFα, z-VAD-fmk [19]

RIP1 inhibitor: Necrostatin1 (Nec-1 )[65];

MLKL inhibitor: necrosulfonamide (NSA) [65];

RIPK3 inhibitors: GSK872, HS-1371 [65]

Autophagy-dependent cell death

Formation of double-membraned autolysosomes, including macroautophagy, microautophagy and chaperone-mediated autophagy [61]

MAP 1 LC3B-I to MAP 1LC3B-II conversion; increased autophagic flux and lysosomal activity [5, 22]

Beclin 1, ATG family proteins, LC3, DRAM3, TFEB, Na⁺/K⁺-ATPase, AMPK, mTOR [5, 19, 22, 66]

Rapamycin, lithium, sodium, valproate, carbamazepine [67]

Non-selective PI3K inhibitors: 3-methyladenine, LY294002, wortmannin;

Selective VPS34 inhibitors: PIK-III, compound 31, SAR 405, Vps34-In1;

Specific ULK1 inhibitors: MRT68921, MRT67307, SBI-0206965;

Specific Beclin1 inhibitors: Spautin-1 Lysosome inhibitors: chloroquine, hydrochloroquin;

lysosomal inhibitor: Chloroquine;

H⁺-ATPase inhibitors: bafilomycin A1, concanamycin A;

USP10 and USP13 inhibitor: spautin 1 [22, 68]

Pyroptosis

Lack of cell swelling; rupture of plasma membrane; bubbling; moderate chromatin condensation [61]

Activation of CASP1, CASP4, CASP5 (CASP1 and CASP11 in mice) and GSDMD; GSDMD cleavage; GSDMD-N–induced pore formation; IL1β and IL18 release [69]

CASP1, CASP4, CASP5 (CASP1 and CASP11 in mice) and GSDMD, GPX4, ESCRT-III, PKA [70]

Metformin, anthocyanin, DHA, DPP8/9 inhibitor, α-NETA, cisplatin, paclitaxel, iron, L61H10, BI2536, lobaplatin, doxorubicin [69]

CASP1 inhibitors: Ac-YVAD-cmk, Z-YVAD (OMe)-FMK, VX765;

CASP11 inhibitor: wedelolactone;

NLRP3-inflammasome inhibitors: MCC950, isoliquiritigenin, glybenclamide, CY-09, oridonin;

GSDMD cleavage inhibitor: Ac-FLTD-CMK [22]