ArticlePLoS pathogens2016
A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- Kinetoplast-Directed Therapies: A Selective Mitochondrial Approach to Combat Leishmaniasis.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Review
- Manipulation of macrophage signaling byVirulence · 2025Review
- TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen.Nature communications · 2025Article
- Ascorbate peroxidase modulation confirms key role in Leishmania infantum oxidative defence.Parasites & vectors · 2024Article
- From classical approaches to new developments in genetic engineering of live attenuated vaccine against cutaneous leishmaniasis: potential and immunization.Frontiers in public health · 2024Review
- Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-AttenuatedMicroorganisms · 2023Review
- Mitochondrial Imbalance ofACS omega · 2022Article
- Hemoglobin Endocytosis and Intracellular Trafficking: A Novel Way of Heme Acquisition byPathogens (Basel, Switzerland) · 2022Review
- Nutrient sensing in Leishmania: Flagellum and cytosol.Molecular microbiology · 2021Review
- The Paradox of a Phagosomal Lifestyle: How Innate Host Cell-Frontiers in immunology · 2021Review
- Sterol 14-α-demethylase is vital for mitochondrial functions and stress tolerance in Leishmania major.PLoS pathogens · 2020Article
- Adaptive iron utilization compensates for the lack of an inducible uptake system in Naegleria fowleri and represents a potential target for therapeutic intervention.PLoS neglected tropical diseases · 2020Article
- Iron and Heme Metabolism at the Leishmania-Host Interface.Trends in parasitology · 2020Review
- Ascorbate-Dependent Peroxidase (APX) from Leishmania amazonensis Is a Reactive Oxygen Species-Induced Essential Enzyme That Regulates Virulence.Infection and immunity · 2019Article
- 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
- Deciphering the Role Played by Autophagy inFrontiers in immunology · 2019Review
- Article
- Emerging therapeutic targets for treatment of leishmaniasis.Expert opinion on therapeutic targets · 2018Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Iron, an essential co-factor of respiratory chain proteins, is critical for mitochondrial function and maintenance of its redox balance. We previously reported a role for iron uptake in differentiation of Leishmania amazonensis into virulent amastigotes, by a mechanism that involves reactive oxygen species (ROS) production and is independent of the classical pH and temperature cues. Iron import into mitochondria was proposed to be essential for this process, but evidence supporting this hypothesis was lacking because the Leishmania mitochondrial iron transporter was unknown. Here we describe MIT1, a homolog of the mitochondrial iron importer genes mrs3 (yeast) and mitoferrin-1 (human) that is highly conserved among trypanosomatids. MIT1 expression was essential for the survival of Trypanosoma brucei procyclic but not bloodstream forms, which lack functional respiratory complexes. L. amazonensis LMIT1 null mutants could not be generated, suggesting that this mitochondrial iron importer is essential for promastigote viability. Promastigotes lacking one LMIT1 allele (LMIT1/Δlmit1) showed growth defects and were more susceptible to ROS toxicity, consistent with the role of iron as the essential co-factor of trypanosomatid mitochondrial superoxide dismutases. LMIT1/Δlmit1 metacyclic promastigotes were unable to replicate as intracellular amastigotes after infecting macrophages or cause cutaneous lesions in mice. When induced to differentiate axenically into amastigotes, LMIT1/Δlmit1 showed strong defects in iron content and function of mitochondria, were unable to upregulate the ROS-regulatory enzyme FeSOD, and showed mitochondrial changes suggestive of redox imbalance. Our results demonstrate the importance of mitochondrial iron uptake in trypanosomatid parasites, and highlight the role of LMIT1 in the iron-regulated process that orchestrates differentiation of L. amazonensis into infective amastigotes.
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