Table 1.
Programmed cell death | Morphological features and key pathway components | References |
---|---|---|
Apoptosis | Nuclear and cytoplasmic condensation (pyknosis), formation of extracellular vesicles (apoptotic bodies) and phagocytosis by surrounding cells. Pro-apoptotic proteins of the BCL-2 family, MOMP, caspase activation (e.g. Apaf-1 in intrinsic apoptosis or FADD in extrinsic apoptosis), cleavage of caspase substrates and ROS production. |
(Kerr et al., 1972) (Li et al., 1997) (Stennicke et al., 1998) |
Necroptosis | Cell swelling, rupture of the plasma membrane, swelling of the cytoplasmic organelles and release of intracellular contents. Inhibition of caspase-8, activation of RIPK1 and RIPK3, formation of the necrosome complex, phosphorylation of MLKL, inflammatory response and release of DAMPs (also called PAMPs in pathogenically infected cells). |
(Degterev et al., 2005) (Li and Beg, 2000) (Holler et al., 2000) |
Pyroptosis | Cell swelling or lack of cell swelling, rupture of the plasma membrane and release of intracellular contents (inflammation-related). Activation of the inflammasome, cleavage of the GSDMD protein, release of pro-inflammatory cytokines (e.g. IL-18). |
(Cookson and Brennan, 2001) (Moujalled et al., 2021) (Galluzzi et al., 2018) |
Autophagy | Vacuolization of the cytoplasm, formation of autophagosomes, without chromatin condensation. ATG family proteins and the conversion of LC3-I to LC3-II (e.g. ATG7 and ATG3 are involved in the phosphorylation and lipidation of LC3 and promote the conversion). |
(Mizushima and Komatsu, 2011) (Bergmann, 2007) |
Ferroptosis | Mitochondria that appear smaller than normal, with increased membrane density. Excessive accumulation of iron, peroxidation of membrane lipids and glutathione depletion. |
(Dixon et al., 2012) (Stockwell, 2022) |
B-cell lymphoma gene 2 (BCL-2), Mitochondrial outer membrane permeabilization (MOMP), Apoptotic peptidase activating factor 1 (Apaf-1), FAS-associated death domain (FADD), Reactive oxygen species (ROS), Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) activation, Mixed lineage kinase domain-like protein (MLKL), Damage-associated molecular patterns (DAMPs), Gasdermin D (GSDMD), Interleukin-18 (IL-18), Autophagy-related protein (ATG), Microtubule-associated protein 1A/1B-light chain 3 (LC3).