Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
Cell Death Dis. 2018 Nov 13;9(11):1129. doi: 10.1038/s41419-018-1173-x.
We show that 3-morpholinosydnonimine (SIN-1)-induced nitric oxide (NO) triggers the formation of SGs. Whereas the composition of NO-induced SGs is initially similar to sodium arsenite (SA)-induced type I (cytoprotective) SGs, the progressive loss of eIF3 over time converts them into pro-death (type II) SGs. NO-induced SG assembly requires the phosphorylation of eIF2α, but the transition to type II SGs is temporally linked to the mTOR-regulated displacement of eIF4F complexes from the m guanine cap. Whereas SA does not affect mitochondrial morphology or function, NO alters mitochondrial integrity and function, resulting in increased ROS production, decreased cytoplasmic ATP, and plasma membrane permeabilization, all of which are supported by type II SG assembly. Thus, cellular energy balance is linked to the composition and function of NO-induced SGs in ways that determine whether cells live or die.
我们证明 3-吗啉代-sydnonimine（SIN-1）诱导的一氧化氮（NO）触发 SG 的形成。虽然 NO 诱导的 SG 的组成最初与亚砷酸钠（SA）诱导的 I 型（细胞保护）SG 相似，但随着时间的推移，eIF3 的逐渐丢失将其转化为促死亡（II 型）SG。NO 诱导的 SG 组装需要 eIF2α 的磷酸化，但向 II 型 SG 的转变与 mTOR 调节的 eIF4F 复合物从 m 鸟嘌呤帽的位移在时间上相关。虽然 SA 不影响线粒体形态或功能，但 NO 会改变线粒体的完整性和功能，导致 ROS 产生增加、细胞质 ATP 减少和质膜通透性增加，所有这些都得到 II 型 SG 组装的支持。因此，细胞能量平衡与 NO 诱导的 SG 的组成和功能相关，决定细胞的生死。
