首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Mitochondrial ROS, uncoupled from ATP synthesis, determine endothelial activation for both physiological recruitment of patrolling cells and pathological recruitment of inflammatory cells
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Mitochondrial ROS, uncoupled from ATP synthesis, determine endothelial activation for both physiological recruitment of patrolling cells and pathological recruitment of inflammatory cells

机译:从ATP合成的线粒体ROS,确定巡逻细胞的生理招募和炎症细胞病理招募的内皮激活

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摘要

Mitochondrial reactive oxygen species (mtROS) are signaling molecules, which drive inflammatory cytokine production and T cell activation. In addition, cardiovascular diseases, cancers, and autoimmune diseases all share a common feature of increased mtROS level. Both mtROS and ATP are produced as a result of electron transport chain activity, but it remains enigmatic whether mtROS could be generated independently from ATP synthesis. A recent study shed light on this important question and found that, during endothelial cell (EC) activation, mtROS could be upregulated in a proton leak-coupled, but ATP synthesis-uncoupled manner. As a result, EC could upregulate mtROS production for physiological EC activation without compromising mitochondrial membrane potential and ATP generation, and consequently without causing mitochondrial damage and EC death. Thus, a novel pathophysiological role of proton leak in driving mtROS production was uncovered for low grade EC activation, patrolling immunosurveillance cell trans-endothelial migration and other signaling events without compromising cellular survival. This new working model explains how mtROS could be increasingly generated independently from ATP synthesis and endothelial damage or death. Mapping the connections among mitochondrial metabolism, physiological EC activation, patrolling cell migration, and pathological inflammation is significant towards the development of novel therapies for inflammatory diseases and cancers.
机译:线粒体反应性氧物质(MTROS)是信号分子,其驱动炎症细胞因子产生和T细胞活化。此外,心血管疾病,癌症和自身免疫性疾病都分享了MTROS水平增加的共同特征。 MTROS和ATP都是由于电子传输链活动而产生的,但它仍然可以从ATP合成可以独立地产生MTROS。最近的研究揭示了这个重要问题,发现,在内皮细胞(EC)激活期间,MTRO可以在质子泄漏耦合的情况下上调,但是ATP合成 - 解耦的方式。结果,EC可以使MTROS生产用于生理EC活化,而不损害线粒体膜电位和ATP生成,因此不会导致线粒体损伤和EC死亡。因此,对于低级EC活化,巡回免疫辐射细胞跨内皮迁移和其他信号事件,未经损害细胞存活,将质子泄漏在驱动MTROS生产中进行的新的致病物理学作用。这个新的工作模型解释了如何从ATP合成和内皮损伤或死亡越来越多地产生MTROS。映射线粒体代谢,生理EC活化,巡逻细胞迁移和病理炎症的关系对于发育炎性疾病和癌症的新疗法是显着的。

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