Fig. 2

Characteristics of different forms of cell death. A In the apoptosis pathway, several death receptors, such as Fas, TNFR, TRAIL-R, and TLRs, recruit FADD or TRADD to activate caspase-8 and -10. Activated caspase-8/10 facilitates the activation of caspase-3, leading to the induction of apoptosis. Additionally, DNA damage can activate BCL family proteins, facilitating the release of cytochrome C into the cytoplasm, which further induces apoptosis by forming a complex known as the apoptosome. In addition, procaspase-9 contributes to apoptosis. B Necroptosis is triggered by LPS through death receptors such as TNFR1/Fas and TLR3/4 in macrophages. C Ferroptosis is characterized by iron-dependent massive lipid peroxidation, and Cystine/GSH/GPX4 is a classical ferroptosis inhibition system. D In the canonical pyroptosis pathway, DAMP, PAMP, or DNA damage activates caspase-1, which then activates caspase-1 to cleave GSDMD to form GSDMD-N, which binds to membranes and creates pores to induce pyroptosis. In the noncanonical pyroptosis pathway, caspase-4/-5/-11 are activated by direct binding with LPS, which then cleaves GSDMD to induce pyroptosis. TNFR Tumor necrosis factor receptors, TLR Toll-like receptor, TDAIL-R TNF-related apoptosis-inducing ligand receptors, FADD Fas-associated death domain protein, TRADD TNFR1-associated death domain protein, TNFα Tumor necrosis factor-alpha, TRAIL TNF-related apoptosis-inducing ligand, Bax/Bcl-2 RIPK1 Receptor interacting protein kinase 1, GPX4 glutathione peroxidase 4, MLKL Mixed lineage kinase-like, ROS Reactive oxygen species; DAMP Damage-associated molecular pattern, PAMP Pathogen-associated molecular pattern, AIM2 Absent in melanoma 2, LPS Lipopolysaccharide, GSDMD Gasdermin D