Necroptosis is a form of programmed necrosis that is mediated by various cytokines and pattern recognition receptors (PRRs). Cells dying by necroptosis show necrotic phenotypes, including swelling and membrane rupture, and release damage-associated molecular patterns (DAMPs), inflammatory cytokines, and chemokines, thereby mediating extreme inflammatory responses. Studies on gene knockout or necroptosis-specific inhibitor treatment in animal models have provided extensive evidence regarding the important roles of necroptosis in inflammatory diseases. The necroptosis signaling pathway is primarily modulated by activation of receptor-interacting protein kinase 3 (RIPK3), which phosphorylates mixed-lineage kinase domain-like protein (MLKL), mediating MLKL oligomerization. In the necroptosis process, these proteins are fine-tuned by posttranslational regulation via phosphorylation, ubiquitination, glycosylation, and protein–protein interactions. Herein, we review recent findings on the molecular regulatory mechanisms of necroptosis.

坏死性凋亡是一种程序性坏死，由各种细胞因子和模式识别受体 (PRR) 介导。因坏死性凋亡而死亡的细胞表现出坏死表型，包括肿胀和膜破裂，并释放损伤相关分子模式 (DAMP)、炎性细胞因子和趋化因子，从而介导极端炎症反应。在动物模型中对基因敲除或坏死性凋亡特异性抑制剂治疗的研究提供了关于坏死性凋亡在炎症性疾病中的重要作用的广泛证据。坏死性凋亡信号通路主要受受体相互作用蛋白激酶 3 (RIPK3) 的激活调节，RIPK3 磷酸化混合谱系激酶结构域样蛋白 (MLK​​L)，从而介导 MLKL 寡聚化。在坏死性凋亡过程中，这些蛋白质通过磷酸化、泛素化、糖基化和蛋白质-蛋白质相互作用的翻译后调节进行微调。在此，我们回顾了最近关于坏死性凋亡分子调控机制的发现。