Painter Heather J, Morrisey Joanne M, Mather Michael W, Vaidya Akhil B
Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
Nature. 2007 Mar 1;446(7131):88-91. doi: 10.1038/nature05572.
The origin of all mitochondria can be traced to the symbiotic arrangement that resulted in the emergence of eukaryotes in a world that was exclusively populated by prokaryotes. This arrangement, however, has been in continuous genetic flux: the varying degrees of gene loss and transfer from the mitochondrial genome in different eukaryotic lineages seem to signify an ongoing 'conflict' between the host and the symbiont. Eukaryotic parasites belonging to the phylum Apicomplexa provide an excellent example to support this view. These organisms contain the smallest mitochondrial genomes known, with an organization that differs among various genera; one genus, Cryptosporidium, seems to have lost the entire mitochondrial genome. Here we show that erythrocytic stages of the human malaria parasite Plasmodium falciparum seem to maintain an active mitochondrial electron transport chain to serve just one metabolic function: regeneration of ubiquinone required as the electron acceptor for dihydroorotate dehydrogenase, an essential enzyme for pyrimidine biosynthesis. Transgenic P. falciparum parasites expressing Saccharomyces cerevisiae dihydroorotate dehydrogenase, which does not require ubiquinone as an electron acceptor, were completely resistant to inhibitors of mitochondrial electron transport. Maintenance of mitochondrial membrane potential, however, was essential in these parasites, as indicated by their hypersensitivity to proguanil, a drug that collapsed the membrane potential in the presence of electron transport inhibitors. Thus, acquisition of just one enzyme can render mitochondrial electron transport nonessential in erythrocytic stages of P. falciparum.
所有线粒体的起源都可追溯到一种共生关系，这种关系导致了真核生物在一个仅由原核生物构成的世界中出现。然而，这种关系一直处于持续的基因变动中：在不同真核生物谱系中，线粒体基因组不同程度的基因丢失和转移似乎表明宿主与共生体之间正在进行一场“冲突”。属于顶复门的真核寄生虫就是支持这一观点的绝佳例子。这些生物拥有已知最小的线粒体基因组，其组织结构在不同属之间存在差异；其中一个属，隐孢子虫，似乎已经失去了整个线粒体基因组。我们在此表明，人类疟原虫恶性疟原虫的红细胞阶段似乎维持着一条活跃的线粒体电子传递链，仅用于一种代谢功能：再生泛醌，它是二氢乳清酸脱氢酶（嘧啶生物合成的一种必需酶）的电子受体。表达酿酒酵母二氢乳清酸脱氢酶（该酶不需要泛醌作为电子受体）的转基因恶性疟原虫对线粒体电子传递抑制剂完全具有抗性。然而，线粒体膜电位的维持在这些寄生虫中至关重要，这体现在它们对氯胍高度敏感，氯胍是一种在存在电子传递抑制剂时会破坏膜电位的药物。因此，仅获得一种酶就能使线粒体电子传递在恶性疟原虫的红细胞阶段变得不再必要。
