Table 1 Morphological characteristics and key biochemical pathway components of RCD pathways.
RCD types | Cellular morphological features | Key biochemical pathway components | Core characteristic (s) | Caspase-dependent | Pore-forming cause | Inflammation features | Immune features | Ref. |
---|---|---|---|---|---|---|---|---|
Necroptosis | Cytoplasmic swelling, pore formation on cells membranes, loss of plasma membrane integrity, swelling of cytoplasmic organelles, and moderate chromatin condensation. | RIPK1, RIPK3, TRADD, NMEO, caspase-8, and MLKL | Necrosome | √ | MLKL-dependent pores | Inflammatory cell death | Immunogenic cell death | |
Apoptosis | Chromatin condensation, plasma membrane blebbing, apoptotic body formation, nuclear fragmentation, cell shrinkage and pyknosis, and phagocytosis by neighboring cells. | Apaf-1, caspase-3/7/8/9, cytochrome c, Bid/tBid, BAX/BAK, BCL-2, and NF-κb | Apoptotic body | √ | No | non-inflammatory | Immunogenic cell death or tolerogenic cell death | |
Ferroptosis | Cells swelling, pore formation on cells membranes, smaller mitochondria with decreased cristae, elevated mitochondrial membrane densities, and accumulation of lipid peroxides in plasma membranes | Fe2+, GPX4, ROS, PUFAs, ACSL4, LPCAT3, ALOXs, SLC40A1, TF-TFRC, | Iron accumulation and lipid peroxidation | × | Iron-dependent lipid peroxidation | Inflammatory cell death | Immunogenic cell death | |
Cuproptosis | Mitochondrial shrinkage, mitochondrial membrane rupture, reduction in the mitochondrial crest and mitochondrial membrane lysis | Cu+/Cu2+, FDX1, GPX4, SLC31A1, LIAS, ROS, ATP7A/B, GSH | DLAT aggregation and loss of Fe-S cluster | × | No | Undetermined | Immunogenic cell death | |
Pyroptosis | Cell swelling, membrane pores formation, membrane rupture, plasma membrane blebbing, moderately condensed chromatin | NLRP3 inflammasome, caspase-1/3/4/5/11, GSDMD, GSDME, IL-1β, and IL-18 | Inflammasome | √ | GSDMs-dependent pores | Inflammatory cell death | Immunogenic cell death |