van Dooren Giel G, Yeoh Lee M, Striepen Boris, McFadden Geoffrey I
From the Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia,
the School of BioSciences, University of Melbourne, Parkville, Victoria 3010, Australia, and.
J Biol Chem. 2016 Sep 9;291(37):19335-50. doi: 10.1074/jbc.M116.725069. Epub 2016 Jul 25.
Outside of well characterized model eukaryotes, relatively little is known about the translocons that transport proteins across the two membranes that surround the mitochondrion. Apicomplexans are a phylum of intracellular parasites that cause major diseases in humans and animals and are evolutionarily distant from model eukaryotes such as yeast. Apicomplexans harbor a mitochondrion that is essential for parasite survival and is a validated drug target. Here, we demonstrate that the apicomplexan Toxoplasma gondii harbors homologues of proteins from all the major mitochondrial protein translocons present in yeast, suggesting these arose early in eukaryotic evolution. We demonstrate that a T. gondii homologue of Tom22 (TgTom22), a central component of the translocon of the outer mitochondrial membrane (TOM) complex, is essential for parasite survival, mitochondrial protein import, and assembly of the TOM complex. We also identify and characterize a T. gondii homologue of Tom7 (TgTom7) that is important for parasite survival and mitochondrial protein import. Contrary to the role of Tom7 in yeast, TgTom7 is important for TOM complex stability, suggesting the role of this protein has diverged during eukaryotic evolution. Together, our study identifies conserved and modified features of mitochondrial protein import in apicomplexan parasites.
除了特征明确的模式真核生物外,对于跨线粒体周围两层膜转运蛋白质的转运体,我们了解得相对较少。顶复门生物是一类细胞内寄生虫,可在人类和动物中引发重大疾病,且在进化上与酵母等模式真核生物相距甚远。顶复门生物含有一个对寄生虫生存至关重要的线粒体,并且是一个经过验证的药物靶点。在这里,我们证明顶复门生物刚地弓形虫含有酵母中所有主要线粒体蛋白质转运体的同源蛋白,这表明这些转运体在真核生物进化早期就已出现。我们证明线粒体外膜转运体(TOM)复合物的核心成分Tom22的弓形虫同源物(TgTom22)对寄生虫生存、线粒体蛋白质导入以及TOM复合物的组装至关重要。我们还鉴定并表征了Tom7的弓形虫同源物(TgTom7),它对寄生虫生存和线粒体蛋白质导入很重要。与Tom7在酵母中的作用相反,TgTom7对TOM复合物的稳定性很重要,这表明该蛋白质的作用在真核生物进化过程中发生了分化。总之,我们的研究确定了顶复门寄生虫中线粒体蛋白质导入的保守和修饰特征。