ArticleCommunications biology2023
A non-canonical sensing pathway mediates Plasmodium adaptation to amino acid deficiency.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- Isoleucine absence from adult human hemoglobin is mirrored in mosquito proteomes and limits malaria parasite growth.bioRxiv : the preprint server for biology · 2026Article
- Hemoglobin Digestion Genes Are Conserved in Lizard-InfectiveEcology and evolution · 2026Article
- Longitudinal plasma metabolomics reveals a role for taurine in asymptomatic malaria and seasonal persistence.Nature microbiology · 2026Article
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- Mass spectrometry-based metabolomics uncovers distinct metabolic signatures and potential therapeutic targets in Plasmodium knowlesi.PloS one · 2025Article
- tRNA regulation and amino acid usage bias reflect a coordinated metabolic adaptation iniScience · 2024Article
- Infection length and host environment influence on Plasmodium falciparum dry season reservoir.EMBO molecular medicine · 2024Article
- RNA polymerase III is involved in regulatingeLife · 2024Article
- The intersection of hostMicrobiology and molecular biology reviews : MMBR · 2024Review
- Article
- Progeny counter mechanism in malaria parasites is linked to extracellular resources.PLoS pathogens · 2023Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Eukaryotes have canonical pathways for responding to amino acid (AA) availability. Under AA-limiting conditions, the TOR complex is repressed, whereas the sensor kinase GCN2 is activated. While these pathways have been highly conserved throughout evolution, malaria parasites are a rare exception. Despite auxotrophic for most AA, Plasmodium does not have either a TOR complex nor the GCN2-downstream transcription factors. While Ile starvation has been shown to trigger eIF2α phosphorylation and a hibernation-like response, the overall mechanisms mediating detection and response to AA fluctuation in the absence of such pathways has remained elusive. Here we show that Plasmodium parasites rely on an efficient sensing pathway to respond to AA fluctuations. A phenotypic screen of kinase knockout mutant parasites identified nek4, eIK1 and eIK2-the last two clustering with the eukaryotic eIF2α kinases-as critical for Plasmodium to sense and respond to distinct AA-limiting conditions. Such AA-sensing pathway is temporally regulated at distinct life cycle stages, allowing parasites to actively fine-tune replication and development in response to AA availability. Collectively, our data disclose a set of heterogeneous responses to AA depletion in malaria parasites, mediated by a complex mechanism that is critical for modulating parasite growth and survival.
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