Furuya Tetsuya, Kessler Peter, Jardim Armando, Schnaufer Achim, Crudder Christopher, Parsons Marilyn
Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14177-82. doi: 10.1073/pnas.222454899. Epub 2002 Oct 17.
Trypanosomatids, the etiologic agents of sleeping sickness, leishmaniasis, and Chagas' disease, compartmentalize glycolysis within glycosomes, metabolic organelles related to peroxisomes. Here, we identify a trypanosome homologue of PEX14, one of the components of the peroxisomal protein import docking complex. We have used double-stranded RNA interference to target the PEX14 transcript for degradation. Glycosomal matrix protein import was compromised, and both glycolytic bloodstream stage parasites and mitochondrially respiring procyclic stage parasites were killed. Thus, unlike peroxisomes, glycosomes are essential organelles. Surprisingly, procyclic forms, which can grow in the absence of glucose, were killed by PEX14 RNA interference only when simple sugars were present. Thus, interference with glycosome protein import makes glucose toxic to trypanosomes.
锥虫是昏睡病、利什曼病和恰加斯病的病原体，它们将糖酵解分隔在糖体中，糖体是与过氧化物酶体相关的代谢细胞器。在这里，我们鉴定出了过氧化物酶体蛋白输入对接复合体的组成成分之一PEX14的锥虫同源物。我们使用双链RNA干扰来靶向降解PEX14转录本。糖体基质蛋白的输入受到损害，糖酵解的血流阶段寄生虫和进行线粒体呼吸的前循环阶段寄生虫均被杀死。因此，与过氧化物酶体不同，糖体是必需的细胞器。令人惊讶的是，仅在存在单糖时，能在无葡萄糖条件下生长的前循环形式才会被PEX14 RNA干扰杀死。因此，干扰糖体蛋白的输入会使葡萄糖对锥虫产生毒性。
