Itoe Maurice A, Sampaio Júlio L, Cabal Ghislain G, Real Eliana, Zuzarte-Luis Vanessa, March Sandra, Bhatia Sangeeta N, Frischknecht Friedrich, Thiele Christoph, Shevchenko Andrej, Mota Maria M
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Max Planck Institute of Molecular cell Biology and Genetics, 01307 Dresden, Germany.
Cell Host Microbe. 2014 Dec 10;16(6):778-86. doi: 10.1016/j.chom.2014.11.006.
During invasion, Plasmodium, the causative agent of malaria, wraps itself in a parasitophorous vacuole membrane (PVM), which constitutes a critical interface between the parasite and its host cell. Within hepatocytes, each Plasmodium sporozoite generates thousands of new parasites, creating high demand for lipids to support this replication and enlarge the PVM. Here, a global analysis of the total lipid repertoire of Plasmodium-infected hepatocytes reveals an enrichment of neutral lipids and the major membrane phospholipid, phosphatidylcholine (PC). While infection is unaffected in mice deficient in key enzymes involved in neutral lipid synthesis and lipolysis, ablation of rate-limiting enzymes in hepatic PC biosynthetic pathways significantly decreases parasite numbers. Host PC is taken up by both P. berghei and P. falciparum and is necessary for correct localization of parasite proteins to the PVM, which is essential for parasite survival. Thus, Plasmodium relies on the abundance of these lipids within hepatocytes to support infection.
在入侵过程中，疟疾的病原体疟原虫会包裹在一个寄生泡膜（PVM）中，该膜构成了寄生虫与其宿主细胞之间的关键界面。在肝细胞内，每个疟原虫子孢子会产生数千个新的寄生虫，这对脂质产生了很高的需求，以支持这种复制并扩大PVM。在这里，对疟原虫感染的肝细胞的总脂质库进行的全面分析显示，中性脂质和主要膜磷脂磷脂酰胆碱（PC）有所富集。虽然在参与中性脂质合成和脂解的关键酶缺乏的小鼠中感染不受影响，但肝脏PC生物合成途径中限速酶的缺失会显著减少寄生虫数量。宿主PC被伯氏疟原虫和恶性疟原虫摄取，并且是寄生虫蛋白正确定位于PVM所必需的，而这对寄生虫的存活至关重要。因此，疟原虫依赖肝细胞内这些脂质的丰富来支持感染。
