Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Mitochondrion. 2020 Jul;53:140-149. doi: 10.1016/j.mito.2020.05.005. Epub 2020 May 26.
Mitochondria is a dynamic organelle of the cell that can regulate and maintain cellular ATP level, ROS production, calcium signaling and immune response. In order to retain their shape and distribution, mitochondria go through coordinated cycles of fission and fusion. Further, dysfunctional mitochondria are selectively eliminated from the cell via mitophagy to synchronize mitochondrial quality control and cellular homeostasis. In addition, mitochondria when in close proximity with the endoplasmic reticulum can alter the signaling pathways and some recent findings also reveal a direct correlation between the mitochondrial localization in the cell to the immune response elicited against the invading pathogen. These modulations in the mitochondrial network are collectively termed as 'mitochondrial dynamics'. Diverse bacteria, virus and parasitic pathogens upon infecting a cell can alter the host mitochondrial dynamics in favor of their multiplication and this in turn can be a major determinant of the disease outcome. Pharmacological perturbations in these pathways thus could lead to generation of additional therapeutic opportunities. This review will focus on the pathogenic modulation of the host mitochondrial dynamics, specifically during the bacterial infections and describes how dysregulated mitochondrial dynamics facilitates the pathogen's ability to establish efficient infection.
线粒体是细胞中的一种动态细胞器，可以调节和维持细胞内的 ATP 水平、ROS 产生、钙信号和免疫反应。为了保持其形状和分布，线粒体通过协调的分裂和融合循环进行。此外，通过自噬选择性地消除功能失调的线粒体，以协调线粒体质量控制和细胞内稳态。此外，当线粒体与内质网紧密接触时，可以改变信号通路，最近的一些发现还揭示了细胞内线粒体定位与针对入侵病原体引发的免疫反应之间的直接相关性。这些线粒体网络的调节统称为“线粒体动力学”。感染细胞的多种细菌、病毒和寄生虫病原体可以改变宿主的线粒体动力学，有利于它们的繁殖，而这反过来又可能是疾病结果的主要决定因素。因此，这些途径的药理学干扰可能会带来额外的治疗机会。这篇综述将重点讨论宿主线粒体动力学的致病调节，特别是在细菌感染期间，并描述失调的线粒体动力学如何促进病原体建立有效的感染能力。
