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Mitochondria and Fungal Pathogenesis: Drug Tolerance, Virulence, and Potential for Antifungal Therapy
Open accessAbstract
Recently, mitochondria have been identified as important contributors to the virulence and drug tolerance of human fungal pathogens. In different scenarios, either hypo- or hypervirulence can result from changes in mitochondrial function. Similarly, specific mitochondrial mutations lead to either sensitivity or resistance to antifungal drugs. Here, we provide a synthesis of this emerging field, proposing that mitochondrial function in membrane lipid homeostasis is the common denominator underlying the observed effects of mitochondria in drug tolerance (both sensitivity and resistance). We discuss how the contrasting effects of mitochondrial dysfunction on fungal drug tolerance and virulence could be explained and the potential for targeting mitochondrial factors for future antifungal drug development.
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“Mitochondria have essential roles in pathogenicity (46) and antifungal drug resistance (3).”
From Inhibition of Classical and Alternative Modes of Respiration in Candida albicans Leads to Cell Wall Remodeling and Increased Macrophage Recognition (2019) · cites this paper as [3]
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“C. albicans requires mitochondrial function for normal growth, morphogenesis, and virulence (2–4)”
From Inhibition of Classical and Alternative Modes of Respiration in Candida albicans Leads to Cell Wall Remodeling and Increased Macrophage Recognition (2019) · cites this paper as [3]
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“Overall, this is an effect that may have clinical relevance because it is known that oxidative stress reduces microbial pathogenicity by enhanced killing by macrophages [35], as shown for A. fumigatus [36].”
From Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets (2020) · cites this paper as [35]
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Fouché, G. (2021) · theses.fr (ABES) · doi:10.70675/b2bddc22z76f0z4d08z950cz2b03da999efa
Merber, R., Laczi, K., Bende, G., Kazinczi, E., Farkas, A., Maróti, G., Sinka, R., & Galgóczy, L. (2026) · Microbiology Spectrum · doi:10.1128/spectrum.00404-26
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Peng, X. W., Zhang, L., Du, M., Yuan, Q., He, H., Xue, X., Liao, W., Ma, Y. N., Pan, W., & Cai, L. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1906168
Gómez-Gaviria, M., Ramírez-Sotelo, U., & Mora-Montes, H. M. (2026) · Current Clinical Microbiology Reports · doi:10.1007/s40588-026-00278-z
Parra‐Giraldo, C. M., Estrada‐Valbuena, J. J., Vargas‐Casanova, Y., Aldea, I., Clemente, L. F., Gil, C., Martínez‐López, R., & Monteoliva, L. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.19.752827
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Mitochondrial iron homeostasis is required for azole tolerance in Candida albicans
Genechten, W. V., Cornips, G., Jonge, M. D., Vergauwen, R., & Dijck, P. V. (2026) · FEBS Journal · doi:10.1111/febs.70773
Metadata
- Authors
- Shingu-Vazquez, M., & Traven, A.
- Affiliations
- Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia
- Monash University (AU)
- Corresponding author
- Traven, Ana
- ORCID
- Traven, Ana
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2011-11
- Volume
- 10
- Issue
- 11
- Pages
- 1376-1383
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC3209048
- OpenAlex
- W2155416658
- Cited by
- 209
- References
- 91
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 13 · 2023: 18 · 2022: 10 · 2021: 12 · 2020: 17 · 2019: 19 · 2018: 14 · 2017: 11 · 2016: 14 · 2015: 14 · 2014: 9 · 2013: 16 · 2012: 6
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- 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
- mitochondria, fungal pathogenesis, drug tolerance, antifungal resistance, fungal virulence, mitochondrial dysfunction, membrane lipid homeostasis, mitochondrial mutations, antifungal drug development, hypervirulence
- MeSH terms
- Antifungal Agents, Azoles, Candida albicans, Cryptococcus neoformans, Fungi, Humans, Membrane Lipids, Microbial Sensitivity Tests, Mitochondria, Mycoses, Polyenes, Saccharomyces cerevisiae, Drug Resistance, Fungal, Candida glabrata, Mitochondrial Membranes, Drug Discovery
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