Toxoplasma gondii scavenges host-derived lipoic acid despite its de novo synthesis in the apicoplast
Toxoplasma gondii scavenges host-derived lipoic acid despite its de novo synthesis in the apicoplast
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DOI：
10.1038/sj.emboj.7601189
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发表时间：
2006-07-12
期刊：
影响因子：
11.4
通讯作者：
Seeber, Frank
中科院分区：
文献类型：
--
作者：
Crawford, Michael J.;Thomsen-Zieger, Nadine;Seeber, Frank
其他真核生物在线粒体内制造硫辛酸，硫辛酸是几种重要脱氢酶复合物的必要辅助因子，与之相反，我们发现细胞内原生动物弓形虫的质体（顶质体）是唯一的从头合成硫辛酸的位点。然而，针对蛋白质附着的脂酸盐的特异性抗体显示，弓形虫的顶质体和线粒体中都存在脂化蛋白。在缺乏脂肪的培养基中培养感染弓形虫的细胞导致线粒体（但不是顶质体）蛋白质的脂肪化显著降低。在培养基中添加外源脂酸盐可以恢复这种作用，表明寄生虫从宿主中清除这种辅助因子。弓形虫暴露于缺乏脂肪的培养基中的脂酸类似物会导致生长抑制，这表明弓形虫可能对这种辅助因子有营养缺陷。系统发育分析显示，在获得质体后，线粒体脂酸合成酶基因的二次丢失。因此，我们的研究揭示了弓形虫的一种意想不到的代谢缺陷，并提出了宿主线粒体与寄生物液泡的密切相互作用是否与宿主的脂酸供应有关的问题。
In contrast to other eukaryotes, which manufacture lipoic acid, an essential cofactor for several vital dehydrogenase complexes, within the mitochondrion, we show that the plastid (apicoplast) of the obligate intracellular protozoan parasite Toxoplasma gondii is the only site of de novo lipoate synthesis. However, antibodies specific for protein-attached lipoate reveal the presence of lipoylated proteins in both, the apicoplast and the mitochondrion of T. gondii. Cultivation of T. gondii-infected cells in lipoate-deficient medium results in substantially reduced lipoylation of mitochondrial (but not apicoplast) proteins. Addition of exogenous lipoate to the medium can rescue this effect, showing that the parasite scavenges this cofactor from the host. Exposure of T. gondii to lipoate analogues in lipoate-deficient medium leads to growth inhibition, suggesting that T. gondii might be auxotrophic for this cofactor. Phylogenetic analyses reveal the secondary loss of the mitochondrial lipoate synthase gene after the acquisition of the plastid. Our studies thus reveal an unexpected metabolic deficiency in T. gondii and raise the question whether the close interaction of host mitochondria with the parasitophorous vacuole is connected to lipoate supply by the host.