Sun Chen, Zhou Bing
State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Microb Cell. 2016 Apr 14;3(5):196-205. doi: 10.15698/mic2016.05.498.
Artemisinin (ART) or Qinghaosu is a natural compound possessing superior anti-malarial activity. Although intensive studies have been done in the medicinal chemistry field to understand the structure-effect relationship, the biological actions of artemisinin are poorly understood and controversial. Due to the current lack of a genetic amiable model to address this question, and an accidental finding made more than a decade ago during our initial exploratory efforts that yeast can be inhibited by artemisinin, we have since been using the baker's yeast as a model to probe the molecular and cellular properties of artemisinin and its derivatives (ARTs) in living cells. ARTs were found to possess potent and specific anti-mitochondrial properties and, to a lesser extent, the ability to generate a relatively general oxidative damage. The anti-mitochondrial effects of artemisinin were later confirmed with purified mitochondria from malaria parasites. Inside some cells heme appears to be a primary reducing agent and reduction of ARTs by heme can induce a relatively nonspecific cellular damage. The molecular basis of the anti-mitochondrial properties of ARTs remains not well elucidated yet. We propose that the anti-mitochondrial and heme-mediated ROS-generating properties constitute two cellcidal actions of ARTs. This review summarizes what we have learned from yeast about the basic biological properties of ARTs, as well as some key unanswered questions. We believe yeast could serve as a window through which to peek at some of the biological action secrets of ARTs that might be difficult for us to learn otherwise.
青蒿素（ART）或青蒿素是一种具有卓越抗疟活性的天然化合物。尽管在药物化学领域已进行了深入研究以了解其构效关系，但青蒿素的生物学作用仍知之甚少且存在争议。由于目前缺乏合适的基因模型来解决这一问题，并且十多年前我们在初步探索工作中偶然发现酵母可被青蒿素抑制，此后我们一直使用面包酵母作为模型来探究青蒿素及其衍生物（ARTs）在活细胞中的分子和细胞特性。研究发现ARTs具有强大且特异的抗线粒体特性，在较小程度上还具有产生相对普遍氧化损伤的能力。青蒿素的抗线粒体作用后来在疟原虫的纯化线粒体中得到证实。在某些细胞内，血红素似乎是主要的还原剂，血红素对ARTs的还原可诱导相对非特异性的细胞损伤。ARTs抗线粒体特性的分子基础仍未得到很好的阐明。我们提出，抗线粒体特性和血红素介导的活性氧生成特性构成了ARTs的两种细胞杀伤作用。本综述总结了我们从酵母研究中了解到的ARTs的基本生物学特性，以及一些关键的未解决问题。我们相信酵母可以作为一个窗口，透过它窥探ARTs的一些生物学作用奥秘，否则这些奥秘可能很难为我们所了解。
