Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mol Microbiol. 2013 Feb;87(4):713-29. doi: 10.1111/mmi.12089. Epub 2013 Jan 21.
In an RNAi library screen for loss of kinetoplast DNA (kDNA), we identified an uncharacterized Trypanosoma brucei protein, named TbLOK1, required for maintenance of mitochondrial shape and function. We found the TbLOK1 protein located in discrete patches in the mitochondrial outer membrane. Knock-down of TbLOK1 in procyclic trypanosomes caused the highly interconnected mitochondrial structure to collapse, forming an unbranched tubule remarkably similar to the streamlined organelle seen in the bloodstream form. Following RNAi, defects in mitochondrial respiration, inner membrane potential and mitochondrial transcription were observed. At later times following TbLOK1 depletion, kDNA was lost and a more drastic alteration in mitochondrial structure was found. Our results demonstrate the close relationship between organelle structure and function in trypanosomes.
在针对动基体 DNA(kDNA)缺失的 RNAi 文库筛选中,我们鉴定到一种未知的布鲁氏锥虫蛋白,命名为 TbLOK1,该蛋白对于维持线粒体的形态和功能是必需的。我们发现 TbLOK1 蛋白位于线粒体外膜的离散斑块中。在锥虫前鞭毛体中敲低 TbLOK1 会导致高度互联的线粒体结构崩溃,形成一条无分支的小管,与血液阶段中看到的流线型细胞器非常相似。在 RNAi 之后,观察到线粒体呼吸、内膜电位和线粒体转录的缺陷。在 TbLOK1 耗尽后的后期,kDNA 丢失,并发现线粒体结构发生更剧烈的改变。我们的结果表明细胞器结构和功能在锥虫中密切相关。