Table 1.

Hallmarks of major types of regulated cell death.

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