Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions

Table 1 The unique morphological and biochemical hallmarks of regulated cell deaths

		Morphological characteristics	Biochemical hallmarks
Apoptotic RCD	Apoptosis	Cell and nucleus shrinkage, nuclear chromatin condensation, karyorrhexis, the formation of apoptotic bodies, and cell fragmentation	↑CASPs (8, 9, 3, and 7), ↑BAD and BAX, ↓BCL2
Non-apoptotic RCDs	Pyroptosis	Inflammasomes caused membrane rupture, cell swelling/cell lysis, DNA fragmentation, nuclear condensation, and nuclear pores	↑CASPs (1 and 7), ↑GSDMs (D, E, etc.), ↑IL-18, ↑IL-1β
	Ferroptosis	Cell swelling, mitochondria shrinkage, cristae disappearance, increased density of mitochondrial membrane, the rupture of the outer mitochondrial membrane	↑Fe2+, ROS, lipid peroxidation, ↑ACSL4 and PTGS2, ↓GPX4 and GSH
	Necroptosis	Organelles swelling, cell membrane rupture, cell lysis, loss of cell membrane integrity, nuclear chromatin deficiency	↑RIPK1, ↑RIPK3, ↑MLKL, ↓CASP-8

RIPK1: Receptor-interacting protein kinase 1; MLKL: Mixed lineage kinase domain-like pseudokinase; RCD: Regulated cell death; CASP: Caspase; ROS: Reactive oxygen species; GSDM: Gasdermin; IL: Interleukin; ACSL4: Acyl-CoA synthetase long-chain family member 4; GPX4: Glutathione peroxidase 4; GSH: Glutathione.