Table 1.

Core molecular mechanisms of various cell death modes

Cell death modalities	Date	The core molecular mechanisms	Reference(s)
Disulfidptosis	2023	When the NADPH supply is limited by glucose deprivation conditions, high cystine uptake in cells with high SLC7A11 expression results in intracellular NADPH depletion, the excessive accumulation of cystine and other disulfide molecules, and abnormal disulfide bond formation in actin cytoskeleton proteins, culminating in actin network collapse and disulfidptosis. (Fig. 1)	[2, 4, 6, 9, 16, 28–32]
Alkaliptosis	2018	The molecular mechanisms underlying alkaliptosis involve pH-induced alkalization, mainly through the activation of JTC801, and the downregulation of carbonic anhydrase 9 (CA9), which depends on the IKBKB-NF-κB pathway, can induce the occurrence of alkaliptosis. (Fig. 2)	[32–34]
Oxeiptosis	2018	Oxeiptosis is a novel type of caspase-independent cell death that is initiated by oxygen radicals and is regulated by the KEAP1-PGAM5-AIFM1 pathway. (Fig. 3)	[32, 35, 36]
Autophagy	2013	Autophagy is a widespread degradation/recycling system in eukaryotic cells that uses the lysosomal system to degrade damaged long-lived proteins and organelles into small molecules such as amino acids, nucleotides, and free fatty acids that can be reused, providing cells with raw materials and energy for the synthesis of new proteins and organelles. (Fig. 4)	[32, 37–42]
Ferroptosis	2012	Due to ferrous iron and lipoxygenase, unsaturated fatty acids on the cell membrane undergo lipid peroxidation, concomitant with the downregulation of the intracellular antioxidant system. This confluence of events collectively promotes ferroptosis. (Fig. 5)	[27, 31, 32, 40, 41, 43–47]
Parthanatos	2009	Activation of NMDA receptors stimulates nNOS-mediated generation of ONOO−, this factor and ROS damage DNA strands, thereby activating PARP-1. When the DNA damage is high, the excessive activation of PARP-1 leads to abundant PAR polymer formation in the nucleus; some of the PARy lated carrier proteins exit the nucleus and cause the release of AIF from a pool on the outer mitochondrial membrane. Once in the cytosol, AIF can bind to MIF. Together, they enter the nucleus and produce large-scale DNA degradation and cell death. (Fig. 6)	[31, 32, 40, 45–51]
Entosis	2007	Entotic cell death is a form of "cannibalism" in which phagocytic cells engulf target cells through entosis, and then under the action of lysosomes, target cells within the entotic vesicles are gradually decomposed into small fragments, which are released into the cytoplasm, ultimately leading to the death of the target cells. Cell adhesion and cytoskeleton rearrangement pathways (such as actin, myosin, RHOA, and ROCK) play important roles in controlling the induction of entosis. In addition to cell adhesion and cytoskeleton rearrangement pathways, other signaling molecules and regulatory factors (such as CDC42) participate in the regulation of entosis through different mechanisms	[32, 40, 42, 52]
Necroptosis	2005	FASL, TRAIL, TNF and IFN-1 activates its receptor, and MLKL, RIPK1 and RIPK3 are recruited to assemble the necrosome through phosphorylation. The phosphorylation-mediated activation of MLKL and subsequent MLKL-mediated membrane pore formation results in necroptosis. In response to TNF-α induced necroptosis, PGAM5 is recruited to the RIPK1/RIPK3 complex on the outer mitochondrial membrane, where it triggers Drp1-mediated mitochondrial fragmentation, which is considered an obligatory step in necroptosis. (Fig. 7)	[31, 32, 40–42, 45, 51, 53]
NETosis	2004	NETosis is a form of cell death driven by NETs that mainly involves NADPH oxidase-mediated ROS production and histone citrullination. These processes eventually lead to chromatin decondensation, nuclear membrane destruction, and the release of chromatin fibers. ROS production and histone citrullination are key regulatory factors in NETosis. (Fig. 8)	[32, 40, 47, 54]
Pyroptosis	2001	Pyroptosis is a form of programmed cell death triggered by inflammasomes that mainly depends on the activation of caspase. Activated caspase cleaves the GSDM protein and releases its N-terminal domain, which binds membrane lipids and perforates the cell membrane, resulting in changes in cell osmotic pressure. The cell then expands until the cell membrane bursts, resulting in scorched cells. (Fig. 9)	[31, 32, 40, 41, 45, 46, 51, 55–59]
Lysosome-dependent cell death	2000	Lysosome-dependent cell death is triggered by ROS or lipid metabolites, and an increase in ROS is one of the main triggers of the increase in calcium, which can occur through the hyperactivation of TRPM2, calcium efflux from lysosomes, leading to LMP, and the release of cathepsins into cytosol. Cathepsins catalyze multiple substrates, including Bid and apoptotic proteins and initiate caspase-dependent cell death. In addition, ER stress can induce cytosolic calcium increase. High cytosolic calcium stimulates the activation of calpain, leading to the degradation of lysosomal membrane proteins such as LAMP1/2, causing lysosomes to rupture and resulting in lysosome-dependent cell death. (Fig. 10)	[32, 40, 45, 47, 60]
Apoptosis	1972	Apoptosis is an active and orderly cell death process determined by genes. When cells encounter internal and external environmental factors, suicide protection measures regulated by genes are initiated to remove nonessential cells or cells that are about to undergo specialization in the body. During this process, cells are shed from the body or lyse to form several apoptotic bodies, which are quickly cleared by macrophages or neighboring cells. Apoptosis is divided into exogenous apoptosis and endogenous apoptosis. It mainly includes the death receptor pathway and the mitochondrial pathway. The death receptor pathway is initiated by the binding of death receptors on the cell surface to ligands, while the mitochondrial pathway activates apoptotic enzymes by releasing proapoptotic factors such as cytochrome C from mitochondria	[32, 40, 42, 45, 61]