Laboratory of Bacteriology, NIAID, NIH, Hamilton, Montana, USA.
Department of Biomedical Sciences, Western Michigan Universitygrid.268187.2 Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA.
mSphere. 2022 Dec 21;7(6):e0042322. doi: 10.1128/msphere.00423-22. Epub 2022 Oct 26.
Mitochondria are critical cellular organelles that perform a wide variety of functions, including energy production and immune regulation. To perform these functions, mitochondria contain approximately 1,500 proteins, the majority of which are encoded in the nuclear genome, translated in the cytoplasm, and translocated to the mitochondria using distinct mitochondrial targeting sequences (MTS). Bacterial proteins can also contain MTS and localize to the mitochondria. For the obligate intracellular human pathogen Chlamydia trachomatis, interaction with various host cell organelles promotes intracellular replication. However, the extent and mechanisms through which Chlamydia cells interact directly with mitochondria remain unclear. We investigated the presence of MTS in the C. trachomatis genome and discovered 30 genes encoding proteins with around 70% or greater probability of mitochondrial localization. Five are translocated to the mitochondria upon ectopic expression in HeLa cells. Mass spectrometry of isolated mitochondria from infected cells revealed that two of these proteins localize to the mitochondria during infection. Comparison of mitochondria from infected and uninfected cells suggests that chlamydial infection affects the mitochondrial protein composition. Around 125 host proteins were significantly decreased or absent in mitochondria from infected cells. Among these were proapoptotic factors and those related to mitochondrial fission/fusion dynamics. Conversely, 82 host proteins were increased in or specific to mitochondria of infected cells, many of which act as antiapoptotic factors and upregulators of cellular metabolism. These data support the notion that C. trachomatis specifically targets host mitochondria to manipulate cell fate decisions and metabolic function to support pathogen survival and replication. Obligate intracellular bacteria have evolved multiple means to promote their intracellular survival and replication within the otherwise harsh environment of the eukaryotic cell. Nutrient acquisition and avoidance of cellular defense mechanisms are critical to an intracellular lifestyle. Mitochondria are critical organelles that produce energy in the form of ATP and regulate programmed cell death responses to invasive pathogenic microbes. Cell death prior to completion of replication would be detrimental to the pathogen. C. trachomatis produces at least two and possibly more proteins that target the mitochondria. Collectively, C. trachomatis infection modulates the mitochondrial protein composition, favoring a profile suggestive of downregulation of apoptosis.
线粒体是关键的细胞细胞器，执行着广泛的功能，包括能量产生和免疫调节。为了执行这些功能，线粒体包含大约 1500 种蛋白质，其中大多数由核基因组编码，在细胞质中翻译，并使用独特的线粒体靶向序列（MTS）转移到线粒体。细菌蛋白也可以含有 MTS 并定位到线粒体。对于必需的人类病原体沙眼衣原体，与各种宿主细胞细胞器的相互作用促进了细胞内复制。然而，衣原体细胞直接与线粒体相互作用的程度和机制仍不清楚。我们研究了沙眼衣原体基因组中 MTS 的存在，并发现 30 个基因编码具有约 70%或更高线粒体定位概率的蛋白质。其中 5 个在 HeLa 细胞中外源表达时被转移到线粒体。感染细胞分离的线粒体的质谱分析显示，其中两个蛋白质在感染过程中定位于线粒体。感染和未感染细胞的线粒体比较表明，衣原体感染会影响线粒体的蛋白质组成。大约 125 种宿主蛋白在感染细胞的线粒体中显著减少或缺失。其中包括促凋亡因子和与线粒体分裂/融合动力学相关的因子。相反，82 种宿主蛋白在感染细胞的线粒体中增加或特异，其中许多作为抗凋亡因子和细胞代谢的上调因子。这些数据支持这样一种观点，即沙眼衣原体专门针对宿主线粒体，以操纵细胞命运决定和代谢功能，从而支持病原体的存活和复制。 专性细胞内细菌已经进化出多种手段，以促进其在真核细胞恶劣环境中的细胞内生存和复制。营养物质的获取和避免细胞防御机制对细胞内生活方式至关重要。线粒体是产生 ATP 形式能量并调节程序性细胞死亡反应以应对入侵的致病性微生物的关键细胞器。在完成复制之前的细胞死亡对病原体是有害的。沙眼衣原体产生至少两种，可能更多种靶向线粒体的蛋白质。总的来说，沙眼衣原体感染调节了线粒体的蛋白质组成，有利于下调凋亡的特征。
