Document Detail

Plasmodium falciparum responds to amino acid starvation by entering into a hibernatory state.
MedLine Citation:
PMID:  23112171     Owner:  NLM     Status:  MEDLINE    
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 We report that when isoleucine is withdrawn from the culture medium of intraerythrocytic P. falciparum, the parasite slows its metabolism and progresses through its developmental cycle at a reduced rate.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.
Shalon E Babbitt; Lindsey Altenhofen; Simon A Cobbold; Eva S Istvan; Clare Fennell; Christian Doerig; Manuel Llinás; Daniel E Goldberg
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-29
Journal Detail:
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:
Created Date:  2012-11-21     Completed Date:  2013-01-29     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E3278-87     Citation Subset:  IM    
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MeSH Terms
Artemisinins / pharmacology
Carbon / metabolism
Eukaryotic Initiation Factor-2B / metabolism
Gene Expression Profiling
Gene Expression Regulation / drug effects
Genes, Protozoan / genetics
Hibernation* / drug effects
Isoleucine / deficiency*
Metabolome / drug effects
Parasites / drug effects,  genetics,  growth & development
Peptide Hydrolases / metabolism
Phosphorylation / drug effects
Plasmodium falciparum / drug effects,  genetics,  growth & development,  metabolism*
Proteolysis / drug effects
Protozoan Proteins / metabolism
Grant Support
Reg. No./Substance:
0/Artemisinins; 0/Eukaryotic Initiation Factor-2B; 0/Protozoan Proteins; 04Y7590D77/Isoleucine; 7440-44-0/Carbon; EC 3.4.-/Peptide Hydrolases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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