| Plasmodium falciparum responds to amino acid starvation by entering into a hibernatory state. | |
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MedLine Citation:
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PMID: 23112171 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The human malaria parasite Plasmodium falciparum is auxotrophic for most amino acids. Its amino acid needs are met largely through the degradation of host erythrocyte hemoglobin; however the parasite must acquire isoleucine exogenously, because this amino acid is not present in adult human hemoglobin. We report that when isoleucine is withdrawn from the culture medium of intraerythrocytic P. falciparum, the parasite slows its metabolism and progresses through its developmental cycle at a reduced rate. Isoleucine-starved parasites remain viable for 72 h and resume rapid growth upon resupplementation. Protein degradation during starvation is important for maintenance of this hibernatory state. Microarray analysis of starved parasites revealed a 60% decrease in the rate of progression through the normal transcriptional program but no other apparent stress response. Plasmodium parasites do not possess a TOR nutrient-sensing pathway and have only a rudimentary amino acid starvation-sensing eukaryotic initiation factor 2α (eIF2α) stress response. Isoleucine deprivation results in GCN2-mediated phosphorylation of eIF2α, but kinase-knockout clones still are able to hibernate and recover, indicating that this pathway does not directly promote survival during isoleucine starvation. We conclude that P. falciparum, in the absence of canonical eukaryotic nutrient stress-response pathways, can cope with an inconsistent bloodstream amino acid supply by hibernating and waiting for more nutrient to be provided. |
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Authors:
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Shalon E Babbitt; Lindsey Altenhofen; Simon A Cobbold; Eva S Istvan; Clare Fennell; Christian Doerig; Manuel Llinás; Daniel E Goldberg |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-10-29 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 109 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-21 Completed Date: 2013-01-29 Revised Date: 2013-04-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: E3278-87 Citation Subset: IM |
Affiliation:
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Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Artemisinins / pharmacology Carbon / metabolism Eukaryotic Initiation Factor-2B / metabolism Gene Expression Profiling Gene Expression Regulation / drug effects Genes, Protozoan / genetics Hibernation* / drug effects Humans Isoleucine / deficiency* Metabolome / drug effects Parasites / drug effects, genetics, growth & development Peptide Hydrolases / metabolism Phenotype Phosphorylation / drug effects Plasmodium falciparum / drug effects, genetics, growth & development, metabolism* Proteolysis / drug effects Protozoan Proteins / metabolism Starvation |
| Grant Support | |
ID/Acronym/Agency:
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1DP2OD001315/OD/NIH HHS; P50 GM071508/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Artemisinins; 0/Eukaryotic Initiation Factor-2B; 0/Protozoan Proteins; 73-32-5/Isoleucine; 7440-44-0/Carbon; EC 3.4.-/Peptide Hydrolases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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