Abstract:
Lipid droplets (LDs) are organelles that are central to lipid and energy homeostasis across all eukaryotes. In the malaria-causing parasite Plasmodium falciparum the roles of LDs in lipid acquisition from its host cells and their metabolism are poorly understood, despite the high demand for lipids in parasite membrane synthesis. We systematically characterised LD size, composition and dynamics across the disease-causing blood infection. Applying split fluorescence emission analysis and three-dimensional (3D) focused ion beam-scanning electron microscopy (FIB-SEM), we observed a decrease in LD size in late schizont stages. LD contraction likely signifies a switch from lipid accumulation to lipid utilisation in preparation for parasite egress from host red blood cells. We demonstrate connections between LDs and several parasite organelles, pointing to potential functional interactions. Chemical inhibition of triacylglyerol (TAG) synthesis or breakdown revealed essential LD functions for schizogony and in counteracting lipid toxicity. The dynamics of lipid synthesis, storage and utilisation in P. falciparum LDs might provide a target for new anti-malarial intervention strategies.
摘要:
脂滴(LD)是所有真核生物中脂质和能量稳态的重要细胞器。在引起疟疾的寄生虫恶性疟原虫中,人们对LDs在从其宿主细胞获得脂质及其代谢中的作用知之甚少。尽管寄生虫膜合成中对脂质的需求很高。我们系统地表征了LD尺寸,引起疾病的血液感染的成分和动力学。应用分裂荧光发射分析和三维聚焦离子束扫描电子显微镜,我们观察到LD大小在裂殖体晚期减小。LD收缩可能表示从脂质积累到脂质利用的转换,以准备寄生虫从宿主红细胞中排出。我们展示了LD和几个寄生虫细胞器之间的联系,指向潜在的功能相互作用。三酰甘油(TAG)合成或分解的化学抑制作用揭示了LD对裂裂和抵消脂质毒性的基本功能。脂质合成的动力学,恶性疟原虫LDs的储存和利用可能为新的抗疟疾干预策略提供目标。