ArticleFrontiers in microbiology2016
A Putative Mitochondrial Iron Transporter MrsA in Aspergillus fumigatus Plays Important Roles in Azole-, Oxidative Stress Responses and Virulence.
Article in Frontiers in microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- The putative mitochondrial serine protease Pim1 regulates azole tolerance through redox homeostasis in Aspergillus fumigatus.Archives of microbiology · 2026Article
- A long non-coding RNA,mSphere · 2026Article
- A long non-coding RNA,bioRxiv : the preprint server for biology · 2026Article
- Resynthesis of Damaged Fe-S Cluster Proteins ProtectsJournal of fungi (Basel, Switzerland) · 2024Article
- Regulatory and pathogenic mechanisms in response to iron deficiency and excess in fungi.Microbial biotechnology · 2023Review
- AnAzf1 acts as a positive regulator of ochratoxin A biosynthesis in Aspergillus niger.Applied microbiology and biotechnology · 2023Article
- Juxtaposing Caenorhabditis elegans-Pathogenic Mould Model with Other Models; How Reliable Is This Nematode Model? A Mini Review.Current microbiology · 2023Review
- Synergistic Antifungal Effect of a Combination of Iron Deficiency and Calcium Supplementation.Microbiology spectrum · 2022Article
- Deletion ofAntimicrobial agents and chemotherapy · 2022Article
- Molecular Characterization and the Essential Biological Function of the Metal Chaperone Protein MtmA in Aspergillus fumigatus.Applied and environmental microbiology · 2022Article
- Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity inFrontiers in microbiology · 2022Article
- The OxrA Protein of Aspergillus fumigatus Is Required for the Oxidative Stress Response and Fungal Pathogenesis.Applied and environmental microbiology · 2021Article
- Mitochondrial perturbation reduces susceptibility to xenobiotics through altered efflux in Candida albicans.Genetics · 2021Article
- The Copper Chaperone CcsA, Coupled with Superoxide Dismutase SodA, Mediates the Oxidative Stress Response in Aspergillus fumigatus.Applied and environmental microbiology · 2021Article
- Azole Resistance in Clinical and EnvironmentalJournal of fungi (Basel, Switzerland) · 2021Article
- Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development.Microorganisms · 2020Review
- Involvement of Mrs3/4 in Mitochondrial Iron Transport and Metabolism inJournal of microbiology and biotechnology · 2020Article
- Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect.mBio · 2020Article
- Aspergillus fumigatus Mitochondrial Acetyl Coenzyme A Acetyltransferase as an Antifungal Target.Applied and environmental microbiology · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Iron is an essential nutrient and enzyme co-factor required for a wide range of cellular processes, especially for the function of mitochondria. For the opportunistic fungal pathogen Aspergillus fumigatus, the ability to obtain iron is required for growth and virulence during the infection process. However, knowledge of how mitochondria are involved in iron regulation is still limited. Here, we show that a mitochondrial iron transporter, MrsA, a homolog of yeast Mrs4p, is critical for adaptation to iron-limited or iron-excess conditions in A. fumigatus. Deletion of mrsA leads to disruption of iron homeostasis with a decreased sreA expression, resulted in activated reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA). Furthermore, deletion of mrsA induces hypersusceptibility to azole and oxidative stresses. An assay for cellular ROS content in ΔmrsA combined with rescue from the mrsA-defective phenotype by the antioxidant reagent L-ascorbic acid indicates that the increased sensitivity of ΔmrsA to the azole itraconazole and to oxidative stress is mainly the result of abnormal ROS accumulation. Moreover, site-directed mutation experiments verified that three conserved histidine residues related to iron transport in MrsA are required for responses to oxidative and azole stresses. Importantly, ΔmrsA causes significant attenuation of virulence in an immunocompromised murine model of aspergillosis. Collectively, our results show that the putative mitochondrial iron transporter MrsA plays important roles in azole- and oxidative-stress responses and virulence by regulating the balance of cellular iron in A. fumigatus.
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