ArticlePLoS pathogens2018
A MFS-like plasma membrane transporter required for Leishmania virulence protects the parasites from iron toxicity.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Ferroptosis in acute kidney injury following crush syndrome: A novel target for treatment.Journal of advanced research · 2023Pooled it
- Glycosomal Aquaglyceroporin 1 dual role in iron homeostasis and antimony susceptibility in Leishmania amazonensis.PLoS neglected tropical diseases · 2026Article
- Repositioning of moxidectin: a promising approach in cutaneous leishmaniasis therapy.Parasite (Paris, France) · 2025Article
- Genetic Iron Overload Hampers Development of Cutaneous Leishmaniasis in Mice.International journal of molecular sciences · 2023Article
- The Escherichia coli MFS-type transporter genes yhjE, ydiM, and yfcJ are required to produce an active bo3 quinol oxidase.PloS one · 2023Article
- A myxozoan genome reveals mosaic evolution in a parasitic cnidarian.BMC biology · 2022Article
- Screening Novel Vaccine Candidates forFrontiers in immunology · 2022Article
- Reporter gene systems: A powerful tool forCurrent research in microbial sciences · 2022Article
- Profilin is involved in G1 to S phase progression and mitotic spindle orientation during Leishmania donovani cell division cycle.PloS one · 2022Article
- Candidates for Balancing Selection in Leishmania donovani Complex Parasites.Genome biology and evolution · 2021Article
- Novel aspects of iron homeostasis in pathogenic bloodstream form Trypanosoma brucei.PLoS pathogens · 2021Article
- Nutrient sensing in Leishmania: Flagellum and cytosol.Molecular microbiology · 2021Review
- Dual transcriptome analysis reveals differential gene expression modulation influenced byMicrobial genomics · 2020Article
- Touching the Surface: Diverse Roles for the Flagellar Membrane in Kinetoplastid Parasites.Microbiology and molecular biology reviews : MMBR · 2020Review
- Iron and Heme Metabolism at the Leishmania-Host Interface.Trends in parasitology · 2020Review
- Intracellular iron availability modulates the requirement for Leishmania Iron Regulator 1 (LIR1) during macrophage infections.International journal for parasitology · 2019Article
- Protean permeases: Diverse roles for membrane transport proteins in kinetoplastid protozoa.Molecular and biochemical parasitology · 2019Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Iron is essential for many cellular processes, but can generate highly toxic hydroxyl radicals in the presence of oxygen. Therefore, intracellular iron accumulation must be tightly regulated, by balancing uptake with storage or export. Iron uptake in Leishmania is mediated by the coordinated action of two plasma membrane proteins, the ferric iron reductase LFR1 and the ferrous iron transporter LIT1. However, how these parasites regulate their cytosolic iron concentration to prevent toxicity remains unknown. Here we characterize Leishmania Iron Regulator 1 (LIR1), an iron responsive protein with similarity to membrane transporters of the major facilitator superfamily (MFS) and plant nodulin-like proteins. LIR1 localizes on the plasma membrane of L. amazonensis promastigotes and intracellular amastigotes. After heterologous expression in Arabidopsis thaliana, LIR1 decreases the iron content of leaves and worsens the chlorotic phenotype of plants lacking the iron importer IRT1. Consistent with a role in iron efflux, LIR1 deficiency does not affect iron uptake by L. amazonensis but significantly increases the amount of iron retained intracellularly in the parasites. LIR1 null parasites are more sensitive to iron toxicity and have drastically impaired infectivity, phenotypes that are reversed by LIR1 complementation. We conclude that LIR1 functions as a plasma membrane iron exporter with a critical role in maintaining iron homeostasis and promoting infectivity in L. amazonensis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.