Table 1.
The morphological and biochemical features of the different types of cell death.
| Ferroptosis | Apoptosis | Autophagy | Necroptosis | |
|---|---|---|---|---|
|
Morphological
Features |
Cell membrane: lack of rupture and blebbing of the plasma membrane, rounding-up of the cell Cytoplasm: small mitochondria with increased mitochondrial membrane densities, reduction or vanishing of mitochondria crista, outer mitochondrial membrane rupture Nucleus: normal nucleus |
Cell membrane: formation of apoptotic bodies and cytoskeletal disintegration Cytoplasm: cellular volume reduction but no significant changes in mitochondrial structure Nucleus: nuclear volume reduction; chromatin agglutination; nuclear fragmentation |
Cell membrane: normal cell membrane Cytoplasm: formation of double-membraned autolysosomes, including macroautophagy, microautophagy and chaperone-mediated autophagy Nucleus: lack of chromatin condensation, |
Cell membrane: plasma membrane breakdown Cytoplasm: generalized swelling of the cytoplasm and organelles Nucleus: moderate chromatin condensation |
|
Biochemical
Features |
Iron accumulation and lipid peroxidation; Inhibition of system Xc- with decreased cystine uptake; Release of arachidonic acid mediators |
Activation of caspases oligonucleosomal DNA fragmentation |
Increased lysosomal activity (e.g., LC3-I to LC3-II conversion) |
Drop in ATP levels; Activation of RIP1, RIP3, and MLKL; Release of DAMPs; PARP1 hyperactivation |
| Core proteins | SLC7A11, Nrf2, HO-1, GPX4, p53, TFR1, VDAC2/3, ACSL4, LOXs |
p53, Bax, Bak, Bcl-2 family proteins |
ATG5, ATG7, Beclin 1 and other ATG family proteins |
RIP1, RIP3, MLKL |
System Xc-: cysteine/glutamate transporter receptor; LC3: microtubule-associated protein 1 light chain 3; ATP: adenosine triphosphate; RIP1: receptor-interacting protein 1; RIP3: receptor-interacting protein 3; MLKL: mixed lineage kinase domain-like protein; DAMPs: damage-associated molecular patterns; PARP1: poly (ADP-ribose) polymerase 1; SLC7A11: solute carrier family 7 member 11; Nrf2: nuclear factor erythroid 2-related factor 2; HO-1: heme oxygenase-1; GPX4: glutathione peroxidase 4; TFR1: transferrin receptor 1; VDAC2/3: voltage-dependent anion channels 2/3, ACSL4: acyl-CoA synthetase long-chain family member 4; LOXs: arachidonate lipoxygenase; Bax: BCL2-associated X protein; Bak: BCL-2 homologous antagonist/killer; ATG5: autophagy protein 5; ATG7: autophagy-related 7.