细胞胀激活了NINJ1,以调节在调节性亡过程中血透的调节
Yves Dondelinger1,2, Dario Priem3,4, Jon Huyghe3,4
1Inflammation Research Center, VIB, Technologiepark 71, 9052, Zwijnaarde-Ghent, Belgium. yves.dondelinger@irc.vib-ugent.be.
Cell death & disease
|November 19, 2023
概括
NINJ1被确定为血透 (PMP) 和与损伤相关的分子模式 (DAMP) 在各种瘤类型中释放的关键调节器. 它的功能独立于已知的毛孔形成分子,并由细胞胀触发.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 血透 (PMP) 对于释放与损伤相关的分子模式 (DAMP) 至关重要,这些模式可以启动无菌炎症.
- 虽然MLKL和GSDMs在死和烧中调解PMP,但其他死形式的机制尚不清楚.
研究的目的:
- 在各种亡途径中识别PMP的新型调节剂.
- 阐明PPP和DAMP释放的机制,超出已知的孔形成蛋白.
主要方法:
- 研究了NINJ1在铁亡,帕尔塔纳托斯,H2O2诱导的亡和二次亡中的作用.
- 评估了NINJ1的功能,独立于MLKL,GSDMD和GSDME.
- 分析了与脂质过氧化和活性氧物种 (ROS) 相关的NINJ1激活.
主要成果:
- 鉴定出NINJ1是多种瘤类型中PMP和DAMP释放的关键调节者.
- NINJ1的膜透活性发生在代谢后的细胞死亡后,并且独立于MLKL,GSDMD和GSDME.
- 细胞胀诱导了NINJ1的寡合化,但一个完整的激活机制还没有被发现.
结论:
- NINJ1是一种新型的,在各种形式的调节性瘤中释放PMP和DAMP的重要调解者.
- NINJ1 作用于铁死触发物的下游,其激活与细胞胀有关,而不仅仅是 ROS.
- 需要进一步的研究才能完全揭示依赖NINJ1的PMP的激活途径.
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