Regulated cell death (RCD) relies on activation and recruitment of pore-forming proteins (PFPs) that function as executioners of specific cell death pathways: apoptosis regulator BAX (BAX), BCL-2 homologous antagonist/killer (BAK) and BCL-2-related ovarian killer protein (BOK) for apoptosis, gasdermins (GSDMs) for pyroptosis and mixed lineage kinase domain-like protein (MLKL) for necroptosis. Inactive precursors of PFPs are converted into pore-forming entities through activation, membrane recruitment, membrane insertion and oligomerization. These mechanisms involve protein–protein and protein–lipid interactions, proteolytic processing and phosphorylation. In this Review, we discuss the structural rearrangements incurred by RCD-related PFPs and describe the mechanisms that manifest conversion from autoinhibited to membrane-embedded molecular states. We further discuss the formation and maturation of membrane pores formed by BAX/BAK/BOK, GSDMs and MLKL, leading to diverse pore architectures. Lastly, we highlight commonalities and differences of PFP mechanisms involving BAX/BAK/BOK, GSDMs and MLKL and conclude with a discussion on how, in a population of challenged cells, the coexistence of cell death modalities may have profound physiological and pathophysiological implications.

受调节的细胞死亡 (RCD) 依赖于作为特定细胞死亡途径执行者的成孔蛋白 (PFP​​) 的激活和募集：细胞凋亡调节剂 BAX (BAX)、BCL-2 同源拮抗剂/杀伤剂 (BAK) 和 BCL-2相关的卵巢杀伤蛋白 (BOK) 用于细胞凋亡，gasdermins (GSDM) 用于细胞焦亡，混合谱系激酶结构域样蛋白 (MLK​​L) 用于细胞坏死。PFP 的非活性前体通过活化、膜募集、膜插入和寡聚化转化为成孔实体。这些机制涉及蛋白质-蛋白质和蛋白质-脂质相互作用、蛋白水解加工和磷酸化。在本综述中，我们讨论了 RCD 相关 PFP 引起的结构重排，并描述了从自抑制分子状态到膜包埋分子状态的明显转化机制。我们进一步讨论了由 BAX/BAK/BOK、GSDM 和 MLKL 形成的膜孔的形成和成熟，从而导致不同的孔结构。最后，我们强调了涉及 BAX/BAK/BOK、GSDM 和 MLKL 的 PFP 机制的共性和差异，并讨论了在一群受攻击的细胞中，细胞死亡模式的共存如何可能具有深远的生理和病理生理学意义。