Table 1.
Type | Morphological changes | Cellular events | Major regulators | Trigger signals |
---|---|---|---|---|
Ferroptosis | Mitochondrial shrinkage and increased mitochondrial membrane density | Iron accumulation; lipid peroxidation; ROS accumulation | Positive: TFRC, LOXs, ACSL4, LPCAT3, ALOX15, GLS2, NCOA4, VDAC2/3, RAS, NOX, TfR1, TP53, GLS2s, BECN1 Negative: GPX4, FSP1, HSPB1/5, SLC7A11, NFS1 |
Iron overload, GSH depletion |
Apoptosis | Cell shrinkage, membrane blebbing, chromatin condensation and DNA fragmentation, formation of apoptotic bodies | Phosphatidylserine exposure; DNA fragment; Caspase activation; mitochondria transmembrane potential dissipation | Positive: initiator caspase (CASP2/8/910); effector caspase (CASP3/6/7); pro-apoptotic BCL2 family; TP53 Negative: anti-apoptotic BCL2 family |
Death receptor activation |
Autophagy | Double-membraned autolysosomes formation | LC3-I to LC3-II conversion; increased autophagic flux and lysosomal activity | Positive:ATG5/7, BECN1 and AMPK Negative: mTOR |
Impaired organelles, oxidative stress |
Pyroptosis | Lack of cell swelling, rupture of plasma membrane and unaffected mitochondrial integrity | Activation of CASP1 and GSDMD; GSDMDN–induced pore formation; IL-1β release | Positive: CASP1, CASP11, and GSDMD Negative: GPX4, ESCRT-III, PKA |
Pathogenic microorganism infection, external stimuli |
Necroptosis | Plasma membrane rupture, moderate chromatin condensation and cell swelling | RIPK1, RIPK3 and MLKL phosphorylation; DAMPs release | Positive: RIPK1/3, MLKL | Activation of TNF superfamily receptors |