Table 1.

Hallmarks of programmed cell death in mammals.

Form	p53	Morphology	Biochemistry
Associated with development
Apoptosis18,19	p53	Cell rounding, nuclear condensation, membrane blebbing, apoptotic bodies	Activates CASP3 and PARP1, DNA fragmentation and loss, ΔΨm dissipation, phosphatidylserine exposure
Anoikis20	p53	Anchorage-dependent cells detach from the extracellular matrix	Cleaved EMC proteins (laminin, fibronectin, vitronectin) → apoptosis
Lysosome dependent21		Plasma membrane repair, lysosome membrane permeabilization	Release of lysosomal hydrolytic enzymes (cathepsins), lysosomal iron-induced oxidative injury
Autophagy dependent22,23	p53	Autophagic vacuolization	LC3-I to LC3-II conversion, increases autophagic flux and lysosomal activity
Associated with disease
Necroptosis24	p53	Cell swells, PMR, moderate chromatin condensation	Activates RIPK1, RIPK3, and MLKL, cytosolic necrosome formation
Oxeiptosis25		Apoptosis-like	ROS-dependent, activates KEAP1 and NFE2L2. caspase-independent, no AIFM1 translocation
Ferroptosis26	p53	Small mitochondria (mt), reduced mt-crista, elevated mt-membrane densities, mt-membrane rupture	Iron accumulates, lipid peroxidation, ΔΨm dissipation, LC3-I to LC3-II conversion, glutaminolysis, caspase-independent
Parthanatos27	p53	Chromatin condensation, large DNA fragments, no cell swelling, apoptotic bodies or small DNA fragments, PMR	Oxidative stress (ROS)-induced, PARP1 activation, ΔΨm dissipation, caspase-independent, NAD+ and ATP depletion, accumulates PARP polymers, AIFM1 translocation
Alkaliptosis28		Necrosis-like	Intracellular alkalinization, activates NF-κB, caspase-independent
Pyroptosis29		No cell swelling, PMR, bubbling, moderate chromatin condensation	Activates CASP1, CASP3, and GSDMD, GSDMD-N-induced pore formation, IL1B released
Entotic30		One cell invades another	Activates adhesion proteins and actomyosin, LC3-associated phagocytosis
Netotic31		PMR, nuclear membrane collapse, chromatin fiber release	Forms NETs, release and translocation of granular enzymes, histone citrullination

Note: ΔΨm is mitochondrial membrane potential.³⁷ Reactive oxygen species is reactive oxygen species. Neutrophil Extracellular Traps (NETs) are neutrophil extracellular traps. LC3 is MAP1LC3B. Dying cells release small vesicular apoptotic bodies.³⁸ Plasma membrane rupture releases intracellular molecules that propagate inflammatory response.³⁹ Apoptosis-inducing factor 1 (AIFM1) translocates from mitochondria to nucleus.⁴⁰ EMC is extracellular matrix. Adapted from Ref. ¹⁷.

NMRs, neutrophil extracellular traps; PARP, poly(ADP-ribose) polymerase; PMR, plasma membrane rupture; ROS, reactive oxygen species.