Mycobacterium tuberculosis (Mtb) employs diverse strategies to survive inside the host macrophages. In this study, we have identified a conserved hypothetical protein of Mtb; Rv0674, which is present in the mitochondria of the host cell. The genetic knock-out of rv0674 (Mtb-KO) showed increased growth of Mtb. The intracellular infection with recombinant Mycobacterium smegmatis (MSMEG) expressing Rv0674 (MS_Rv0674), established that the protein is involved in promoting the apoptotic cell death of the macrophage. To investigate the mechanism incurred in mitochondria, we observed that the protein physically interacts with the control region (D-loop) of the mitochondrial DNA (LSP and HSP promoters of the loop) of the macrophages and facilitates the increased expression of mRNA in all the complexes of mitochondrial encoded OXPHOS subunits. The changes in OXPHOS levels corroborated with the ATP synthesis, mitochondrial membrane potential and superoxide production. The infection with MS_Rv0674 confirmed the role of this protein in effecting the intracellular infection. The fluorescent and confocal microscopy confirmed that the protein is localized in the mitochondria of infected macrophages and in the cells of BAL of TB patients. Together these findings indicate towards the novel function of the protein which is unlike to the earlier established mechanisms of mycobacterial physiology.

中文翻译：

---

分枝杆菌起源蛋白 Rv0674 定位于线粒体，与 D-loop 相互作用并调节 OXPHOS 以促进结核分枝杆菌的细胞内持久性

结核分枝杆菌 (Mtb) 采用多种策略在宿主巨噬细胞内生存。在这项研究中，我们鉴定了一种保守的 Mtb 假设蛋白；Rv0674，存在于宿主细胞的线粒体中。rv0674 (Mtb-KO) 的基因敲除显示 Mtb 的生长增加。用表达 Rv0674 (MS_Rv0674) 的重组耻垢分枝杆菌 (MSMEG) 进行细胞内感染，确定该蛋白质参与促进巨噬细胞的凋亡细胞死亡。为了研究线粒体中发生的机制，我们观察到该蛋白质与巨噬细胞线粒体 DNA（环的 LSP 和 HSP 启动子）的控制区（D 环）发生物理相互作用，并促进所有 mRNA 的表达增加。线粒体编码的 OXPHOS 亚基复合物。OXPHOS 水平的变化证实了 ATP 合成、线粒体膜电位和超氧化物的产生。MS_Rv0674 感染证实了该蛋白质在影响细胞内感染中的作用。荧光和共聚焦显微镜证实该蛋白质位于受感染巨噬细胞的线粒体和结核病患者的 BAL 细胞中。这些发现一起表明蛋白质的新功能，这与早期建立的分枝杆菌生理机制不同。荧光和共聚焦显微镜证实该蛋白质位于受感染巨噬细胞的线粒体和结核病患者的 BAL 细胞中。这些发现一起表明蛋白质的新功能，这与早期建立的分枝杆菌生理机制不同。荧光和共聚焦显微镜证实该蛋白质位于受感染巨噬细胞的线粒体和结核病患者的 BAL 细胞中。这些发现一起表明蛋白质的新功能，这与早期建立的分枝杆菌生理机制不同。