Mitochondrial energy metabolism and its developmental regulation in Trypanosoma

我们对产能内共生体衍生的细胞器（如线粒体和氢化酶体）的相关性和进化的看法，在很大程度上是通过比较它们的代谢形成的。锥虫代表了真核生物进化的一个早枝分支，我们最近的工作表明，它们的能量代谢与通常的看法相反，与高等真核生物有很大的不同。在其他特征中，它们的线粒体与氢化酶体共享乙酰琥珀酰CoA转移酶（ASCT），并将其用于乙酸分泌。我们克隆了第一个ASCT基因，并利用T. brucei系统来研究ASCT表达的遗传操作后的代谢。具有柠檬酸循环酶乌头酸酶的靶向缺失的锥虫在采采蝇中肠中是完全健康的，但在进一步向唾液腺形式发展时显示出戏剧性的发育表型。我们将测试的假设，线粒体能量代谢是从根本上改造的节肢动物宿主环境，窝藏锥虫。比较锥虫线粒体代谢的其他原生生物和调查的适应性和主机控制这种代谢的早期内共生体衍生物的属性都有望揭示一些光。

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.