Mitochondrial energy metabolism and its developmental regulation in Trypanosoma

锥虫线粒体能量代谢及其发育调控

• 批准号: 5435939
• 负责人: Professor Dr. Michael Boshart
• 金额: --
• 依托单位: Institut für Genetik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5435939?language=en
• 关键词: Mitochondrial; energy; metabolism; its; developmental

Our view of the relatedness and evolution of energy producing endosymbiont-derived organelles like mitochondria and hydrogenosomes has been much shaped by the comparison of their metabolism. Trypanosomes represent an early branch of eukaryotic evolution and our recent work shows that their energy metabolism is, in contrast to common belief, much different from higher eukaryotes. Among other features, their mitochondria share with hydrogenosomes the enzyme acetyl succinyl CoA transferase (ASCT) and use it for acetate secretion. We have cloned the first ASCT gene and take advantage of the excellent reverse genetic tools in the T. brucei system to investigate the metabolism upon genetic manipulations of ASCT expression. Trypanosomes with targeted deletion of the citric acid cycle enzyme aconitase are perfectly heathy in the tsetse fly midgut but show a dramatic developmental phenotype upon further progression towards salivary gland forms. We will test the hypothesis that mitochondrial energy metabolism is radically remodeled by the arthropod host environment that harbours the trypanosomes. Comparison of the metabolism of trypanosomatid mitochondria to other protists and investigation of the adaptability and host control of this metabolism are both expected to shed some light on the properties of early endosymbiont derivatives.

通过比较它们的代谢比较，我们对产生能量内共生衍生的细胞器（如线粒体和氢化体）的相关性和演变的看法已经很大程度上了。锥虫代表了真核进化的早期分支，我们最近的工作表明，它们的能量代谢与共同的信念相反，与较高的真核生物有很大不同。除其他特征外，它们的线粒体与氢化体共享乙酰琥珀酰COA转移酶（ASCT），并将其用于乙酸分泌。我们已经克隆了第一个ASCT基因，并利用T. Brucei系统中出色的反向遗传工具来研究ASCT表达遗传操作的代谢。具有针对性缺失柠檬酸循环酶刺激酶靶向缺失的锥虫在采摘蝇中肠中非常健康，但在进一步发展向唾液腺形式的进展后显示出急剧的发育表型。我们将检验以下假设：线粒体能量代谢是通过携带锥虫的节肢动物宿主环境从根本上重塑的。比较锥形线粒体与其他生物的代谢以及对这种新陈代谢的适应性和宿主控制的研究都可以揭示出早期内共生衍生物的特性。