Laboratory of Molecular Pathogenesis, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India.
Front Cell Infect Microbiol. 2020 Sep 30;10:457. doi: 10.3389/fcimb.2020.00457. eCollection 2020.
Mitochondria, are undoubtedly critical organelle of a eukaryotic cell, which provide energy and offer a platform for most of the cellular signaling pathways that decide cell fate. The role of mitochondria in immune-metabolism is now emerging as a crucial process governing several pathological states, including infection, cancer, and diabetes. Mitochondria have therefore been a vulnerable target for several bacterial and viral pathogens to control host machinery for their survival, replication, and dissemination. , a highly successful human pathogen, persists inside alveolar macrophages at the primary infection site, applying several strategies to circumvent macrophage defenses, including control of host mitochondria. The infection and specific mycobacterial factors that enter the host mitochondrial milieu perturb mitochondrial dynamics and function by disturbing mitochondrial membrane potential, shifting bioenergetics parameters such as ATP and ROS, orienting the host cell fate and thereby infection outcome. In the present review, we attempt to integrate the available information and emerging dogmas to get a holistic view of infection vis-a-vis mycobacterial factors that target host mitochondria and changes therein in terms of morphology, dynamics, proteomic, and bioenergetic alterations that lead to a differential cell fate and immune response determining the disease outcome. We also discuss critical host factors and processes that are overturned by , such as cAMP-mediated signaling, redox homeostasis, and lipid droplet formation. Further, we also present alternate dogmas as well as the gaps and limitations in understanding some of the present research areas, which can be further explored by understanding some critical processes during infection and the reasons thereof. Toward the end, we propose to have a set of guidelines for pursuing investigations to maintain uniformity in terms of early and late phase, MOI of infection, infection duration and incubation periods, the strain of mycobacteria, passage numbers, and so on, which all work as probable variables toward different readouts. Such a setup would, therefore, help in the smooth integration of information across laboratories toward a better understanding of the disease and possibilities of host-directed therapy.
线粒体无疑是真核细胞的重要细胞器，它提供能量，并为决定细胞命运的大多数细胞信号通路提供平台。线粒体在免疫代谢中的作用现在作为一个关键过程出现，它控制着几种病理状态，包括感染、癌症和糖尿病。因此，线粒体已成为几种细菌和病毒病原体的脆弱靶点，以控制宿主机制以维持其生存、复制和传播。作为一种高度成功的人类病原体，在原发性感染部位的肺泡巨噬细胞内持续存在，应用几种策略来规避巨噬细胞防御，包括控制宿主线粒体。该感染和进入宿主线粒体环境的特定分枝杆菌因子通过扰乱线粒体膜电位、改变生物能学参数（如 ATP 和 ROS）、改变宿主细胞命运从而改变感染结果来干扰线粒体动力学和功能。在本综述中，我们试图整合现有信息和新兴的教条，以获得宿主线粒体靶向分枝杆菌因子的 感染的整体视图，以及形态、动力学、蛋白质组学和生物能学改变方面的变化，这些变化导致不同的细胞命运和免疫反应，从而决定疾病结果。我们还讨论了被 颠覆的关键宿主因素和过程，如 cAMP 介导的信号转导、氧化还原稳态和脂滴形成。此外，我们还提出了替代的教条以及在理解一些当前研究领域方面的差距和局限性，通过理解 感染过程中的一些关键过程及其原因，可以进一步探索这些领域。最后，我们建议制定一套指导方针，以进行研究，以保持在早期和晚期、感染的 MOI、感染持续时间和潜伏期、分枝杆菌菌株、传代数等方面的一致性，这些都是朝着不同的结果变化的可能变量。因此，这样的设置将有助于实验室之间信息的顺利整合，从而更好地理解疾病和宿主导向治疗的可能性。
