Ferroptosis is a regulated form of necrotic cell death that is caused by the accumulation of oxidized phospholipids, leading to membrane damage and cell lysis^1,2. Although other types of necrotic death such as pyroptosis and necroptosis are mediated by active mechanisms of execution^3,4,5,6, ferroptosis is thought to result from the accumulation of unrepaired cell damage¹. Previous studies have suggested that ferroptosis has the ability to spread through cell populations in a wave-like manner, resulting in a distinct spatiotemporal pattern of cell death^7,8. Here we investigate the mechanism of ferroptosis execution and discover that ferroptotic cell rupture is mediated by plasma membrane pores, similarly to cell lysis in pyroptosis and necroptosis^3,4. We further find that intercellular propagation of death occurs following treatment with some ferroptosis-inducing agents, including erastin^2,9 and C′ dot nanoparticles⁸, but not upon direct inhibition of the ferroptosis-inhibiting enzyme glutathione peroxidase 4 (GPX4)¹⁰. Propagation of a ferroptosis-inducing signal occurs upstream of cell rupture and involves the spreading of a cell swelling effect through cell populations in a lipid peroxide- and iron-dependent manner.

Ferroptosis是一种坏死性细胞死亡的调节形式，它是由氧化磷脂的积累引起的，导致膜损伤和细胞溶解^1,2。尽管其他类型的坏死性死亡（例如，凋亡和坏死性坏死）是通过执行死刑的积极机制^{3、4、5、6}来介导的，但人们认为肥大病是由于未修复的细胞损伤¹的积累所致。先前的研究表明，铁锈病具有以波状方式在细胞群体中传播的能力，从而导致细胞死亡的独特时空模式^7,8。。在这里，我们研究了促肥大作用的执行机制，并发现促肥大细胞的破裂是由质膜孔介导的，类似于热解和坏死性肾炎^3,4中的细胞裂解。我们进一步发现，细胞死亡的发生是在用一些促肥大症诱导剂治疗后发生的，其中包括促红细胞生成素^2,9和C'点纳米粒子⁸，但不是直接抑制了促肥大症抑制酶谷胱甘肽过氧化物酶4（GPX4）¹⁰。促铁作用的信号的传播发生在细胞破裂的上游，并且涉及细胞溶胀作用在脂质过氧化物和铁依赖性的方式下通过细胞群传播。