Matz Joachim Michael
Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; Centre for Structural Systems Biology, 22607 Hamburg, Germany.
Trends Parasitol. 2022 Jul;38(7):525-543. doi: 10.1016/j.pt.2022.02.010. Epub 2022 Mar 19.
During intraerythrocytic growth, the human malaria parasite Plasmodium falciparum degrades up to 80% of the host cell's hemoglobin inside an acidified organelle called the digestive vacuole (DV). Here, the globin chains are broken down by a number of proteases, while heme is detoxified through biomineralization, a process that is targeted by several potent antimalarial drugs. This review explores our current understanding of the DV, including the digestion of hemoglobin, the sequestration of heme, and the functions of lipids and transporters of the DV membrane. Furthermore, the mechanisms of drug action inside the DV and the molecular adaptations that mediate resistance are discussed.
在红细胞内生长过程中，人类疟原虫恶性疟原虫会在一个被称为消化液泡（DV）的酸化细胞器内降解高达80%的宿主细胞血红蛋白。在这里，球蛋白链被多种蛋白酶分解，而血红素则通过生物矿化作用进行解毒，这一过程是几种强效抗疟药物的作用靶点。本综述探讨了我们目前对消化液泡的理解，包括血红蛋白的消化、血红素的隔离以及消化液泡膜的脂质和转运蛋白的功能。此外，还讨论了消化液泡内药物作用的机制以及介导耐药性的分子适应性。
