PROTEIN IMPORTERS OF TRYPANOSOMA BRUCI MITOCHONDRIAL OUTER MEMBRANE

布氏锥虫线粒体外膜的蛋白质输入者

• 批准号: 6485266
• 负责人: Minu Chaudhuri
• 金额: $ 17.91万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6485266
• 关键词: Trypanosoma; genetic library; genetic regulation; laboratory rabbit; laboratory rat; membrane transport proteins; mitochondrial membrane; molecular chaperones; molecular cloning; protein transport

Blood borne parasitic diseases are major causes of human morbidity and mortality, particularly in the tropical world. African trypanosomes, the protozoa of the Trypanosoma brucei complex, are such parasites that live extracellularly in the blood and tissue fluids of the vertebrate host, utilizing blood glucose as their sole source of energy eventually leading to hypoglycemia dn disease syndrome known as African sleeping sickness. Mitochondrial biogenesis is an essential part of the digenetic life cycle of this protozoa. These cells suppress their mitochondrial activities when they live in the bloodstream of its mammalian host. During blood-meal, parasites are transferred to the insect gut and they regenerate their mitochondrial activities. Import of a vast majority of nuclear encoded mitochondrial protein is a necessary process for mechanisms in African trypanosomes so as to understand their role sin mitochondrial biogenesis. The initial requirement to accomplish this goal is the isolation and characterization of the trypanosome proteins involved in mitochondrial protein import. The specific aims of this proposal are: (i) to clone and mitochondrial membrane from T. brucei; (ii) to identify and characterize different cytosolic and mitochondrial chaperone proteins involved in this import process; and (iii) to assess the roles of these cloned proteins in protein important during mitochondrial biogenesis of this parasite. Characterization of the mitochondrial import machinery in this parasite may provide insight into genetic control mechanism in trypanosomes where, in contrast to most eukaryotes, developmental regulation of gene expression is almost entirely post-transcriptional. Understanding of this developmental process will elucidate one of the major aspects of trypanosomal parasitism. This in turn will help us to design rational trypanocidal chemotherapeutic strategies.

血液传播的寄生虫疾病是人类发病率和死亡率的主要原因，尤其是在热带世界中。非洲锥虫是布鲁氏锥虫菌群的原生动物，是这种寄生虫，细胞外生活在脊椎动物宿主的血液和组织液中，将血糖作为其唯一的能量来源，最终导致低血糖症DN疾病DN疾病综合症综合症已知的非洲疾病。线粒体生物发生是该原生动物的二试生命周期的重要组成部分。这些细胞生活在其哺乳动物宿主的血液中时抑制其线粒体活性。在血液中，寄生虫被转移到昆虫肠道上，并再生其线粒体活性。进口绝大多数核编码的线粒体蛋白是非洲锥虫机制的必要过程，以了解其作用，以理解其罪线粒体生物发生。 实现这一目标的最初要求是分离和表征参与线粒体蛋白导入的锥虫蛋白。该提议的具体目的是：（i）从T. Brucei的克隆和线粒体膜； （ii）识别和表征参与此进口过程的不同胞质和线粒体伴侣蛋白； （iii）评估这些克隆蛋白在该寄生虫的线粒体生物发生过程中重要的蛋白质中的作用。线粒体进口机械在该寄生虫中的表征可以提供对锥虫中遗传控制机制的见解，与大多数真核生物相比，基因表达的发育调节几乎完全是转录后的。了解这一发展过程将阐明锥虫寄生虫的主要方面之一。反过来，这将有助于我们设计合理的锥虫化学治疗策略。