阻断反向电子转移介导的线粒体DNA氧化,可以从PANoptosis中拯救细胞
Fu-Li Shi1, Qing Li1, Rong Xu1
1Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Acta pharmacologica Sinica
|November 14, 2023
概括
反向电子运输 (RET) 和线粒体ROS驱动PANoptosis. 像MPMS和DMF这样的抗RET试剂通过阻断mtDNA氧化来抑制PANoptosis,为炎症性疾病提供潜在的治疗方法.
科学领域:
- 细胞死亡生物学 细胞死亡生物学
- 免疫学 免疫学 免疫学
- 线粒体生物学 线粒体生物学
背景情况:
- 泛亡是一种新的细胞死亡途径,与炎症性疾病有关.
- 通过反向电子运输 (RET) 生成的线粒体反应性氧物种 (mtROS) 有助于热和死.
- 在PANoptosis中mtROS和RET的作用尚未完全阐明.
研究的目的:
- 研究mtROS和RET在PANoptosis中的作用.
- 探索抗RET试剂在抑制PANoptosis中的治疗潜力.
主要方法:
- 使用TGF-β激活激酶1 (TAK1) 抑制剂 (5Z-7-oxozeaenol) 加上脂多糖 (LPS) 诱导巨细胞中的PANoptosis.
- 评估了抗RET试剂 (1-甲氧PMS和二甲基烟酸) 对PANoptosis,mtROS产生和PANoptosome形成的影响.
- 用一个HLH小鼠模型来评估抗RET试剂的体内疗效.
主要成果:
- 使用抗RET试剂 (MPMS或DMF) 的预处理剂量依赖地抑制了巨细胞中的Oxo/LPS诱导的PANoptosis.
- MPMS和DMF抑制了PANoptosis信号传递和PANoptosome形成的所有三个臂.
- RET和mtROS是由Oxo/LPS诱导的,而MPMS/DMF则逆转了这种情况,这也阻止了mtROS和PANoptosome的形成.
- 抗RET试剂减轻了小鼠的HLH病变,减少了肝脏和脏中的PANoptosis标志物.
结论:
- RET和线粒体DNA氧化是PANoptosis的关键诱导因素.
- 抗RET试剂 (MPMS,DMF) 是一种新型的PANoptosis抑制剂.
- 这些发现突显了抗RET策略在治疗与PANoptosis相关的炎症性疾病方面的潜力.
相关概念视频
01:46Electron Transport Chain: Complex I and II
14.2K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
14.2K
01:45Mitochondrial Membranes
11.2K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
11.2K
01:30The Electron Transport Chain
16.8K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.8K