在大肠炎中,CKMT1缺乏导致线粒体功能障碍,并通过逆电子转移衍生的ROS促进肠上皮细胞亡
Zhijie Wang1,2,3,4, Haicong Wu1,3,5, Xin Chang1,3,4
1National Clinical Research Center for Digestive Diseases, Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China.
Cell death & disease
|March 16, 2025
概括
肌酸激酶线粒体1 (CKMT1) 通过维护线粒体功能和肠道屏障完整性来预防性结肠炎. 失去CKMT1会加剧肠道的炎症和亡.
科学领域:
- 分子生物学分子生物学
- 胃肠病学 胃肠病学
- 线粒体生物学 线粒体生物学
背景情况:
- 线粒体功能障碍与性结肠炎 (UC) 的病原发生有关.
- 肌酸激酶线粒体1 (CKMT1),参与能量代谢,在肠道炎症中起到未知的作用.
研究的目的:
- 调查CKMT1在炎症期间肠上皮细胞 (IEC) 中的作用.
- 阐明CKMT1在炎症性肠病 (IBD) 背景下影响线粒体平衡和亡的机制.
主要方法:
- 分析UC患者结肠组织中的CKMT1表达和硫酸 (DSS) 诱导的大肠炎小鼠模型.
- 产生和研究肠上皮特异性的CKMT1淘汰小鼠.
- 使用IEC进行体外实验以评估亡途径和反应性氧物种 (ROS) 生成.
主要成果:
- 在UC患者和DSS诱导的大肠炎小鼠的结肠组织中,CKMT1的表达显著下降.
- 在IEC中CKMT1淘汰会损害线粒体平衡,屏障功能,增加氧化应激和亡.
- CKMT1缺乏通过反向电子转移 (RET) 增强了TNF-α诱导的线粒体ROS,导致mPTP开放和亡.
结论:
- CKMT1在维持肠道平衡和线粒体功能方面发挥着至关重要的作用.
- CKMT1通过限制ROS的产生和亡来防止肠道炎症.
- CKMT1代表了炎症性肠病 (IBD) 的潜在治疗标.
更多相关视频
06:31Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
Published on: June 2, 2023
924
08:37Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
16.4K
相关概念视频
Electron Transport Chain: Complex I and II
9.9K
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...
9.9K
The Inner Mitochondrial Membrane
3.2K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.2K
Mitochondrial Membranes
6.9K
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,...
6.9K
The Electron Transport Chain
15.9K
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...
15.9K
