Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30606, USA.
Int J Mol Sci. 2020 Dec 7;21(23):9316. doi: 10.3390/ijms21239316.
The mitochondrial Ca uptake in trypanosomatids shares biochemical characteristics with that of animals. However, the composition of the mitochondrial Ca uniporter complex (MCUC) in these parasites is quite peculiar, suggesting lineage-specific adaptations. In this work, we compared the inhibitory activity of ruthenium red (RuRed) and Ru360, the most commonly used MCUC inhibitors, with that of the recently described inhibitor Ru265, on , the agent of Chagas disease. Ru265 was more potent than Ru360 and RuRed in inhibiting mitochondrial Ca transport in permeabilized cells. When dose-response effects were investigated, an increase in sensitivity for Ru360 and Ru265 was observed in -KO and -KO cells as compared with control cells. In the presence of RuRed, a significant increase in sensitivity was observed only in -KO cells. However, application of Ru265 to intact cells did not affect growth and respiration of epimastigotes, mitochondrial Ca uptake in Rhod-2-labeled intact cells, or attachment to host cells and infection by trypomastigotes, suggesting a low permeability for this compound in trypanosomes.
锥虫的线粒体 Ca 摄取具有与动物相似的生化特征。然而，这些寄生虫的线粒体 Ca 单向转运体复合物（MCUC）的组成非常特殊，表明存在谱系特异性的适应。在这项工作中，我们比较了常用的 MCUC 抑制剂钌红（RuRed）和 Ru360 与最近描述的抑制剂 Ru265 对克氏锥虫（引起恰加斯病的病原体）的抑制活性。Ru265 在通透细胞中抑制线粒体 Ca 转运的活性强于 Ru360 和 RuRed。当研究剂量反应效应时，与对照细胞相比，在 -KO 和 -KO 细胞中观察到 Ru360 和 Ru265 的敏感性增加。在 RuRed 存在的情况下，仅在 -KO 细胞中观察到敏感性显著增加。然而，将 Ru265 应用于完整细胞不会影响滋养体的生长和呼吸、Rhod-2 标记的完整细胞中的线粒体 Ca 摄取或游离体对宿主细胞的附着和感染，表明该化合物在锥虫中的通透性较低。
