坏死传统上被认为是一种被动的、无调节的细胞死亡。然而，越来越多的证据表明，坏死和凋亡一样，可以通过基因控制和高度调控的细胞过程来执行，其形态学特征是细胞膜完整性丧失、细胞内细胞器和/或整个细胞肿胀(肿瘤)(Rello S et al. 2005;Galluzzi L et al. 2007;Berghe TV et al. 2014;Ros U et al. 2020)。坏死死亡的形态学特征与不同形式的程序性细胞死亡有关，包括(但不限于)单细胞死亡、坏死、谷氨酸诱导的催产症、铁下垂、炎性小体介导的坏死等。每一种都可以在一定的病理生理条件下触发。例如，UV、ROS或烷基化剂可诱导聚(adp -核糖)聚合酶1 (PARP1)过度激活(parthanatos)，而肿瘤坏死因子(TNF)或toll样受体配体(LPS和dsRNA)可触发坏死小体介导的坏死。启动事件,例如,PARP1 hyperactivation, necrosome形成,激活NADPH氧化酶类,依次触发一个或多个NAD +和ATP-depletion等常见的细胞内信号,增强Ca2 +涌入,失调的氧化还原状态,增加产量的活性氧(ROS)和磷脂酶的活性。这些信号影响细胞器和细胞膜，导致渗透膨胀、大量能量消耗、脂质过氧化和溶酶体膜完整性的丧失。 Different mechanisms of permeabilization have emerged depending on the cell death form. Pore formation by gasdermins (GSDMs) is a hallmark of pyroptosis, while mixed lineage kinase domain-like (MLKL) protein facilitates membrane permeabilization in necroptosis, and phospholipid peroxidation leads to membrane damage in ferroptosis. This diverse repertoire of mechanisms leading to membrane permeabilization contributes to define the specific inflammatory and immunological outcome of each type of regulated necrosis. Regulated or programmed necrosis eventually leads to cell lysis and release of cytoplasmic content into the extracellular region that is often associated with a tissue damage resulting in an intense inflammatory response.

Reactome模块描述了坏死和焦亡。