The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites.
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 isoprenoid...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3784473?pdf=render |
| _version_ | 1818359376093642752 |
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| author | Jolyn E Gisselberg Teegan A Dellibovi-Ragheb Krista A Matthews Gundula Bosch Sean T Prigge |
| author_facet | Jolyn E Gisselberg Teegan A Dellibovi-Ragheb Krista A Matthews Gundula Bosch Sean T Prigge |
| author_sort | Jolyn E Gisselberg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T20:43:54Z |
| format | Article |
| id | doaj.art-a9ed6a1eabf24ceb8aaa99934584e594 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-13T20:43:54Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a9ed6a1eabf24ceb8aaa99934584e5942022-12-21T23:32:05ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0199e100365510.1371/journal.ppat.1003655The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites.Jolyn E GisselbergTeegan A Dellibovi-RaghebKrista A MatthewsGundula BoschSean T PriggeThe 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.http://europepmc.org/articles/PMC3784473?pdf=render |
| spellingShingle | Jolyn E Gisselberg Teegan A Dellibovi-Ragheb Krista A Matthews Gundula Bosch Sean T Prigge The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. PLoS Pathogens |
| title | The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. |
| title_full | The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. |
| title_fullStr | The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. |
| title_full_unstemmed | The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. |
| title_short | The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. |
| title_sort | suf iron sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites |
| url | http://europepmc.org/articles/PMC3784473?pdf=render |
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