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Cited by 32Fungal Infections and StudiesFungal and yeast genetics researchMitochondrial Function and Pathology

Connecting iron regulation and mitochondrial function in Cryptococcus neoformans

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Horianopoulos, Linda C, Kronstad, James W·2019·Current Opinion in Microbiology
DOI 10.1016/j.mib.2019.04.002PMC PMC6842668
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Abstract

Iron acquisition is essential for the proliferation of microorganisms, and human pathogens such as the fungus Cryptococcus neoformans must use sophisticated uptake mechanisms to overcome host iron sequestration. Iron is of particular interest for C. neoformans because its availability is an important cue for the elaboration of virulence factors. In fungi, extracellular iron is taken up through high affinity, low affinity, siderophore-mediated, and heme uptake pathways, and the details of these mechanisms are under active investigation in C. neoformans. Following uptake, iron is transported to intracellular organelles including mitochondria where it is used in heme biosynthesis and the synthesis of iron-sulfur (Fe-S) cluster precursors. One Fe-S cluster binding protein of note is the monothiol glutaredoxin Grx4 which has emerged as a master regulator of iron sensing in C. neoformans and other fungi through its influence on the expression of proteins for iron uptake or use. The activity of Grx4 likely occurs through interactions with Fe-S clusters and transcription factors known to control expression of the iron-related functions. Although the extent to which Grx4 controls the iron regulatory network is still being investigated in C. neoformans, it is remarkable that it also influences the expression of many genes encoding mitochondrial functions. Coupled with recent studies linking mitochondrial morphology and electron transport to virulence factor elaboration, there is an emerging appreciation of mitochondria as central players in cryptococcal disease.

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  • In pathogenic fungi such as Aspergillus fumigatus and Cryptococcus neoformans, mitochondria enhance host adaptability through nutrient sensing, stress regulation, and immune evasion, and the drug-resistant phenotype of C. albicans is closely related to mitochondrial functional status.

    “Notably, in pathogenic fungi such as Aspergillus fumigatus and Cryptococcus neoformans, mitochondria enhance host adaptability through mechanisms such as nutrient sensing, stress regulation, and immune evasion [41–43], and the drug-resistant phenotype of C. albicans has also been shown to be closely related to mitochondrial functional status [44].”

    From Mitochondrial anchor protein Num11 is key to pathogenicity of <i>Candida albicans</i> by affecting mitochondrial function and cell wall masking (2025) · cites this paper as [41]

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Authors
Horianopoulos, L. C., & Kronstad, J. W.
Affiliations
University of British Columbia (CA)
Corresponding author
Kronstad, James W
ORCID
Venue
Current Opinion in Microbiology
Publisher
Elsevier BV
Published
2019-12
Volume
52
Pages
7-13
ISSN
1369-5274 (ISSN-L)
DOI
10.1016/j.mib.2019.04.002
PMC
PMC6842668
OpenAlex
W2947851404
Cited by
32
References
57
Citations by year
2026: 8 · 2025: 4 · 2024: 7 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 7 · 2019: 1
FWCI
0.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Microbiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
Cryptococcus neoformans, iron regulation, iron acquisition, siderophores, heme uptake, mitochondrial function, iron-sulfur clusters, iron sensing, heme biosynthesis, mitochondrial morphology, electron transport, virulence factors, fungal pathogenesis
MeSH terms
Biological Transport, Cryptococcus neoformans, Iron, Iron-Sulfur Proteins, Mitochondria, Trace Elements, Gene Expression Regulation, Fungal, Metabolic Networks and Pathways, Glutaredoxins

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