Dephospho-CoA kinase, a nuclear-encoded apicoplast protein, remains active and essential after Plasmodium falciparum apicoplast disruption.
Dephospho-CoA kinase, a nuclear-encoded apicoplast protein, remains active and essential after Plasmodium falciparum apicoplast disruption.
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DOI：
10.15252/embj.2020107247
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发表时间：
2021-08-16
期刊：
影响因子：
--
通讯作者：
Prigge ST
中科院分区：
文献类型：
--
作者：
Swift RP;Rajaram K;Liu HB;Prigge ST
疟原虫含有一种称为顶质体的重要细胞器，它容纳脂肪酸、血红素、类异戊二烯和铁硫簇合成的代谢途径。令人惊讶的是，只要在生长培养基中补充类异戊二烯前体焦磷酸异戊二烯（IPP），疟原虫就可以在没有顶质体的情况下存活，这使得类异戊二烯的合成似乎是血期疟原虫细胞器的唯一基本功能。在这里描述的工作中，我们将一种负责辅酶A合成的酶DPCK定位到顶质体上，但即使在IPP存在的情况下，我们也无法删除DPCK。然而，一旦内源性DPCK与大肠杆菌DPCK （EcDPCK）互补，我们就成功地删除了它。然后，我们能够证明，通过敲低补充的EcDPCK，寄生虫的生存需要DPCK活性。此外，我们发现，在顶质体破裂后的囊泡中，DPCK酶活性仍然具有功能和必要。这些结果表明，虽然血期恶性疟原虫的顶质体可以被破坏，但所产生的囊泡仍然具有生物化学活性，能够完成基本功能。在血期疟原虫中，辅酶A的产生是顶质体细胞器不可缺少的功能。
Malaria parasites contain an essential organelle called the apicoplast that houses metabolic pathways for fatty acid, heme, isoprenoid, and iron–sulfur cluster synthesis. Surprisingly, malaria parasites can survive without the apicoplast as long as the isoprenoid precursor isopentenyl pyrophosphate (IPP) is supplemented in the growth medium, making it appear that isoprenoid synthesis is the only essential function of the organelle in blood‐stage parasites. In the work described here, we localized an enzyme responsible for coenzyme A synthesis, DPCK, to the apicoplast, but we were unable to delete DPCK, even in the presence of IPP. However, once the endogenous DPCK was complemented with the E. coli DPCK (EcDPCK), we were successful in deleting it. We were then able to show that DPCK activity is required for parasite survival through knockdown of the complemented EcDPCK. Additionally, we showed that DPCK enzyme activity remains functional and essential within the vesicles present after apicoplast disruption. These results demonstrate that while the apicoplast of blood‐stage P. falciparum parasites can be disrupted, the resulting vesicles remain biochemically active and are capable of fulfilling essential functions. Production of coenzyme A is an indispensable function of the apicoplast organelle in blood‐stage malaria parasites.
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