The Toxoplasma Apicoplast Phosphate Translocator Links Cytosolic and Apicoplast Metabolism and Is Essential for Parasite Survival

被引:99
作者
Brooks, Carrie F. [2 ]
Johnsen, Hanne [1 ]
van Dooren, Giel G. [2 ]
Muthalagi, Mani [2 ]
Lin, San San [4 ]
Bohne, Wolfgang [4 ]
Fischer, Karsten [1 ]
Striepen, Boris [2 ,3 ]
机构
[1] Univ Tromso, Inst Biol, N-9037 Tromso, Norway
[2] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA
[3] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA
[4] Univ Gottingen, Inst Med Microbiol, D-37075 Gottingen, Germany
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
APICOMPLEXAN PARASITES; PLASMODIUM-FALCIPARUM; ESCHERICHIA-COLI; DRUG TARGET; LIPOIC ACID; MOLECULAR CHARACTERIZATION; ISOPRENOID BIOSYNTHESIS; MALARIA PARASITES; GENOME SEQUENCE; GENE FAMILY;
D O I
10.1016/j.chom.2009.12.002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Apicomplexa. are unicellular eukaryotic pathogens that carry a vestigial algal endosymbiont, the apicoplast. The physiological function of the apicoplast and its integration into parasite metabolism remain poorly understood and at times controversial. We establish that the Toxoplasma apicoplast membrane-localized phosphate translocator (TgAPT) is an essential metabolic link between the endosymbiont and the parasite cytoplasm. TgAPT is required for fatty acid synthesis in the apicoplast, but this may not be its most critical function. Further analyses demonstrate that TgAPT also functions to supply the apicoplast with carbon skeletons for additional pathways and, indirectly, with energy and reduction power. Genetic ablation of the transporter results in rapid death of parasites. The dramatic consequences of loss of its activity suggest that targeting TgAPT could be a viable strategy to identify antiparasitic compounds.
引用
收藏
页码:62 / 73
页数:12
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