The role of neutral lipid nanospheres in Plasmodium falciparum haem crystallization

被引:167
作者
Pisciotta, John M.
Coppens, Isabelle
Tripathi, Abhai K.
Scholl, Peter F.
Shuman, Joel
Bajad, Sunil
Shulaev, Vladimir
Sullivan, David J., Jr.
机构
[1] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA
[2] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA
[3] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA
关键词
haem crystallization; haemozoin; lipidomics; malaria; neutral lipid; Plasmodium falciparum; quinoline;
D O I
10.1042/BJ20060986
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The intraerythrocytic malaria parasite constructs an intracellular haem crystal, called haemozoin, within an acidic digestive vacuole where haemoglobin is degraded. Haem crystallization is the target of the widely used antimalarial quinoline drugs. The intracellular mechanism of molecular initiation of haem crystallization, whether by proteins, polar membrane lipids or by neutral lipids, has not been fully substantiated. In the present study, we show neutral lipid predominant nanospheres, which envelop haemozoin inside Plasmodium falciparum digestive vacuoles. Subcellular fractionation of parasite-derived haemozoin through a dense 1.7 M sucrose cushion identifies monoacylglycerol and diacylglycerol neutral lipids as well as some polar lipids in close association with the purified haemozoin. Global MS lipidomics detects monopalmitic glycerol and monostearic glycerol, but not mono-oleic glycerol, closely associated with haemozoin. The complex neutral lipid mixture rapidly initiates haem crystallization, with reversible pH-dependent quinotine inhibition associated with quinoline entry into the neutral lipid microenvironment. Neutral lipid nanospheres both enable haem crystallization in the presence of high globin concentrations and protect haem from H2O2 degradation. Conceptually, the present study shifts the intracellular microenvironment of haem crystallization and quinoline inhibition from a polar aqueous location to a non-polar neutral lipid nanosphere able to exclude water for efficient haem crystallization.
引用
收藏
页码:197 / 204
页数:8
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