Mycobacterium tuberculosis virulence correlates with mitochondrial cytochrome c release in infected macrophages
Mycobacterium tuberculosis virulence correlates with mitochondrial cytochrome c release in infected macrophages
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DOI：
10.1046/j.1365-3083.2003.01318.x
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发表时间：
2003-10-01
影响因子：
3.7
通讯作者：
Sánchez-García, FJ
中科院分区：
文献类型：
--
作者：
Abarca-Rojano, E;Rosas-Medina, P;Sánchez-García, FJ
线粒体是参与能量产生、细胞存活和凋亡的分子事件的中心。线粒体膜电位（Deltapsi（m））由细胞分解代谢反应和电子传递链（细胞色素c是其中的一个组成部分）维持，而质子泄漏途径、ATP合成和周转消耗它。在细胞凋亡中观察到线粒体改变，如Deltapsi（m）下降、肿胀和细胞色素c释放。然而，在细胞内感染过程中，线粒体功能的信息缺乏，这一过程肯定会引起宿主细胞的压力。这项工作分析了两种相反毒力的分枝杆菌菌株在感染早期对小鼠巨噬细胞线粒体的影响。结果发现，结核分枝杆菌H37Ra和M.结核病H37Rv容易诱导Deltapsi（m）以及超微结构水平的线粒体形态的变化。此外，在感染后24 h，两株M.结核有趣的是，只有M。结核分枝杆菌H37Rv能够诱导细胞色素c从线粒体释放到胞质溶胶中，从而表明在结核分枝杆菌中存在细胞色素c。结核病H37Rv的特异性因子能够调节细胞色素c易位。细胞色素c释放在分枝杆菌感染中的确切作用仍有待阐明。
Mitochondria are at the centre of molecular events involved in energy production, cell survival and apoptosis. Mitochondrial membrane potential (Deltapsi(m)) is maintained by cellular catabolic reactions and the electron transport chain of which cytochrome c is a constituent, whereas the proton leak pathway, ATP synthesis and turnover consume it. Mitochondrial alterations such as a drop in Deltapsi(m), swelling and cytochrome c release have been observed in apoptosis. However, there is a paucity of information concerning mitochondrial function in the course of intracellular infections, a process that must certainly induce stress on the host cell. This work analyses the effect that two strains of mycobacteria of opposing virulence have on the mitochondria of murine macrophages in the early stages of infection. It was found that infection of J774 cells with both Mycobacterium tuberculosis H37Ra and M. tuberculosis H37Rv readily induced changes in Deltapsi(m) as well as in mitochondrial morphology at the ultrastructural level. In addition, an increase in cytosolic ATP was found at 24 h post infection with both strains of M. tuberculosis. Interestingly, only M. tuberculosis H37Rv was able to induce cytochrome c release from mitochondria to the cytosol, thus suggesting the occurrence in M. tuberculosis H37Rv of a specific factor(s) capable of regulating cytochrome c translocation. The precise role of cytochrome c release in the context of a mycobacterial infection remains to be elucidated.