The plasma membrane is made of glycerophospholipids that separate the inner and outer parts of the cell. Under physiological conditions, it acts as a barrier and gatekeeper to protect cells from the environment. In pathological situations, it undergoes structural and functional changes, resulting in cell damage. Indeed, plasma membrane damage caused by various stresses (e.g., hypoxia, nutritional deficiencies, ultraviolet radiation, and chemotherapeutic agents) is one of the hallmarks of cell death. Phosphatidylserine exposure and plasma membrane blebbing usually occurs in apoptotic cells, while necrotic cells lose the integrity of the plasma membrane and thereby release intracellular damage-associated molecular patterns. In contrast, the endosomal sorting complex required for transport-III (ESCRT-III), an evolutionarily conserved protein complex with membrane fission machinery, plays a key role in the repair of damaged plasma membranes in various types of regulated cell death, such as necroptosis, pyroptosis, and ferroptosis. These emerging findings indicate that ESCRT-III is a potential target to overcome drug resistance during tumor therapy.

质膜由甘油磷脂制成，将细胞的内部和外部分开。在生理条件下，它充当屏障和看门人，保护细胞免受环境影响。在病理情况下，它会发生结构和功能变化，导致细胞损伤。事实上，由各种压力（例如缺氧、营养缺乏、紫外线辐射和化学治疗剂）引起的质膜损伤是细胞死亡的标志之一。磷脂酰丝氨酸暴露和质膜起泡通常发生在凋亡细胞中，而坏死细胞失去质膜的完整性，从而释放细胞内损伤相关的分子模式。相比之下，运输-III (ESCRT-III) 所需的内体分选复合物，一种具有膜裂变机制的进化上保守的蛋白质复合物，在修复各种类型的受调节细胞死亡（如坏死性凋亡、细胞焦亡和铁死亡）中受损的质膜中起着关键作用。这些新发现表明 ESCRT-III 是克服肿瘤治疗期间耐药性的潜在靶点。