Singh Kuldeep, Veluru Niranjan K, Trivedi Vishal, Gupta Chhitar M, Sahasrabuddhe Amogh A
Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow, PIN-226031, Uttar Pradesh, India.
Mol Microbiol. 2014 Feb;91(3):562-78. doi: 10.1111/mmi.12477. Epub 2014 Jan 3.
Actin-related proteins are ubiquitous actin-like proteins that show high similarity with actin in terms of their amino acid sequence and three-dimensional structure. However, in lower eukaryotes, such as trypanosomatids, their functions have not yet been explored. Here, we show that a novel actin-related protein (ORF LmjF.13.0950) is localized mainly in the Leishmania mitochondrion. We further reveal that depletion of the intracellular levels of this protein leads to an appreciable decrease in the mitochondrial membrane potential as well as in the ATP production, which appears to be accompanied with impairment in the flagellum assembly and motility. Additionally, we report that the mutants so generated fail to survive inside the mouse peritoneal macrophages. These abnormalities are, however, reversed by the episomal gene complementation. Our results, for the first time indicate that apart from their classical roles in the cytoplasm and nucleus, actin-related proteins may also regulate the mitochondrial function, and in case of Leishmania donovani they may also serve as the essential factor for their survival in the host cells.
肌动蛋白相关蛋白是普遍存在的肌动蛋白样蛋白，在氨基酸序列和三维结构方面与肌动蛋白具有高度相似性。然而，在诸如锥虫等低等真核生物中，它们的功能尚未得到探索。在此，我们表明一种新型肌动蛋白相关蛋白（开放阅读框LmjF.13.0950）主要定位于利什曼原虫的线粒体中。我们进一步揭示，该蛋白细胞内水平的缺失会导致线粒体膜电位以及ATP产生显著降低，这似乎伴随着鞭毛组装和运动能力的受损。此外，我们报告称如此产生的突变体无法在小鼠腹腔巨噬细胞内存活。然而，这些异常通过附加型基因互补得以逆转。我们的结果首次表明，肌动蛋白相关蛋白除了在细胞质和细胞核中发挥经典作用外，还可能调节线粒体功能，并且对于杜氏利什曼原虫而言，它们也可能是其在宿主细胞中存活的必需因素。
