RRC ID 35622
Author Gisselberg JE, Dellibovi-Ragheb TA, Matthews KA, Bosch G, Prigge ST.
Title The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites.
Journal PLoS Pathog
Abstract The apicoplast organelle of the malaria parasite Plasmodium falciparum contains metabolic pathways critical for liver-stage and blood-stage development. During the blood stages, parasites lacking an apicoplast can grow in the presence of isopentenyl pyrophosphate (IPP), demonstrating that isoprenoids are the only metabolites produced in the apicoplast which are needed outside of the organelle. Two of the isoprenoid biosynthesis enzymes are predicted to rely on iron-sulfur (FeS) cluster cofactors, however, little is known about FeS cluster synthesis in the parasite or the roles that FeS cluster proteins play in parasite biology. We investigated two putative FeS cluster synthesis pathways (Isc and Suf) focusing on the initial step of sulfur acquisition. In other eukaryotes, these proteins can be located in multiple subcellular compartments, raising the possibility of cross-talk between the pathways or redundant functions. In P. falciparum, SufS and its partner SufE were found exclusively the apicoplast and SufS was shown to have cysteine desulfurase activity in a complementation assay. IscS and its effector Isd11 were solely mitochondrial, suggesting that the Isc pathway cannot contribute to apicoplast FeS cluster synthesis. The Suf pathway was disrupted with a dominant negative mutant resulting in parasites that were only viable when supplemented with IPP. These parasites lacked the apicoplast organelle and its organellar genome--a phenotype not observed when isoprenoid biosynthesis was specifically inhibited with fosmidomycin. Taken together, these results demonstrate that the Suf pathway is essential for parasite survival and has a fundamental role in maintaining the apicoplast organelle in addition to any role in isoprenoid biosynthesis.
Volume 9(9)
Pages e1003655
Published 2013-1-1
DOI 10.1371/journal.ppat.1003655
PMID 24086138
PMC PMC3784473
MeSH Apicoplasts / genetics Apicoplasts / metabolism* Carbon-Sulfur Lyases / genetics Carbon-Sulfur Lyases / metabolism* Humans Iron-Sulfur Proteins / genetics Iron-Sulfur Proteins / metabolism* Plasmodium falciparum / cytology Plasmodium falciparum / genetics Plasmodium falciparum / metabolism* Protozoan Proteins / genetics Protozoan Proteins / metabolism* Terpenes / metabolism
IF 6.218
Times Cited 46
Prokaryotes E. coli JW1670-KC