Understanding the highly divergent mitochondrial ATP synthase in T. gondii

7.项目总结/摘要 顶复门寄生虫是人类最常见和最致命的病原体之一。比如说， T.弓形虫感染估计25%的世界人口和疟原虫属。贡献了近一个 每年死亡百万人。顶复门的一个关键特征是它们能够在各种各样的环境中生存。 当它们在宿主之间转移或进入和离开宿主细胞时，环境。这些细胞的广泛分布 寄生虫的感染能力反映了它们新陈代谢的可塑性，毫无疑问，这是为了让它们生存而进化的。 在不同的宿主生态位中定居 线粒体是真核细胞的代谢中枢。线粒体内的反应必须适应 可用的碳源和细胞能量需求。顶复门寄生虫拥有一个 对这些过程负责。在线粒体内，ATP合酶将质子- 呼吸对ATP合成产生动力，因此在代谢可塑性中起关键作用。 然而，基于序列的搜索未能鉴定出在线粒体中ATP合酶的几个关键亚基。 顶复门的基因组。这说明了ATP合酶和线粒体的功能是如何在一般情况下， 对顶复门生物学知之甚少这项提案的目的是查明失踪的 利用T.弓形虫作为一个模型，并了解这一作用， 酶在线粒体生理学中的作用。该项目还旨在分离线粒体， T.弓形虫，铺平了道路，以前所未有的库存，其蛋白质，DNA和脂质。表征 ATP合酶以及确定线粒体代谢物组将在生物医学领域引起广泛兴趣。 分子寄生虫学这些研究将为不同的顶复门代谢开辟新的视角 并为开发急需的抗寄生虫疗法提供机会。

7. PROJECT SUMMARY/ABSTRACT Apicomplexan parasites are among the most common and deadly pathogens of humans. For example, T. gondii infects an estimated 25% of the world's population and Plasmodium spp. contributes to nearly one million deaths each year. A key feature of apicomplexans is their ability to survive in a wide variety of environments as they transfer between hosts or enter and exit host cells. The wide range of cells that these parasites can infect reflects the plasticity of their metabolism, which undoubtedly evolved to allow their survival within the diverse host niches they colonize. Mitochondria are the metabolic hubs of the eukaryotic cell. Reactions within the mitochondria must adapt to the available carbon sources and the cellular energetic needs. Apicomplexan parasites possess a single mitochondrion responsible for these processes. Within the mitochondria, the ATP synthase couples the proton- motive force generated by respiration to ATP synthesis and thus plays a key role in metabolic plasticity. However, sequence-based searches have failed to identify several key subunits of the ATP synthase in the genome of apicomplexans. This exemplifies how the ATP synthase, and mitochondrial function in general, are poorly understood aspects of apicomplexan biology. The goal of this proposal is to identify the missing components of the apicomplexan ATP synthase by using T. gondii as a model and understand the role that this enzyme plays in mitochondrial physiology. The proposed project also aims to isolate mitochondria from T. gondii, paving the way to an unprecedented inventory of its proteins, DNA, and lipids. Characterizing the ATP synthase as well as determining a mitochondrial metabolome will be of broad interest to the fields of molecular parasitology. These studies will open new perspectives on the divergent apicomplexan metabolism and provide opportunities to develop urgently needed anti-parasitic therapies.