ArticleAntimicrobial agents and chemotherapy2013
Mitochondria influence CDR1 efflux pump activity, Hog1-mediated oxidative stress pathway, iron homeostasis, and ergosterol levels in Candida albicans.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 97 citations in OpenAlex.
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- Molecular frontiers of fungal autophagy: from molecular mechanisms to potential targets for antifungal drug discovery.World journal of microbiology & biotechnology · 2026Review
- Candida auris vacuolar calcium pump mediates fluconazole efflux and resistance evolution.Nature microbiology · 2026Article
- Aloe emodin disrupts Candida albicans mitochondrial iron homeostasis against its hyphal development and oral candidiasis.Applied microbiology and biotechnology · 2026Article
- Ecm19 coordinates mitochondrial fission and cellular redox homeostasis.Redox report : communications in free radical research · 2025Article
- Mss2 shapes the virulence ofVirulence · 2025Article
- MTCH2 Deficiency Promotes E2F4/TFRC-Mediated Ferroptosis and Sensitizes Colorectal Cancer Liver Metastasis to Sorafenib.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Suppressed Protein Translation Caused by MSP-8 Deficiency Determines Fungal Multidrug Resistance with Fitness Cost.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Transcription factor Hap2p regulates antioxidant stress responses to maintain miconazole resistance inMycology · 2025Article
- Uncovering the role of mitochondrial genome in pathogenicity and drug resistance in pathogenic fungi.Frontiers in cellular and infection microbiology · 2025Review
- Exploration of novel mechanisms of azole resistance inAntimicrobial agents and chemotherapy · 2024Article
- The mitochondrial protein Bcs1A regulates antifungal drug tolerance by affecting efflux pump expression in the filamentous pathogenic fungusMicrobiology spectrum · 2024Article
- Metabolic homeostasis in fungal infections from the perspective of pathogens, immune cells, and whole-body systems.Microbiology and molecular biology reviews : MMBR · 2024Review
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- Divergent mitochondrial responses and metabolic signal pathways secure the azole resistance in Crabtree-positive and negativeMicrobiology spectrum · 2024Article
- Identification of the Major Facilitator Superfamily Efflux Pump KpsrMFS inInternational journal of molecular sciences · 2024Article
- Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial dysfunction in Candida albicans is known to be associated with drug susceptibility, cell wall integrity, phospholipid homeostasis, and virulence. In this study, we deleted CaFZO1, a key component required during biogenesis of functional mitochondria. Cells with FZO1 deleted displayed fragmented mitochondria, mitochondrial genome loss, and reduced mitochondrial membrane potential and were rendered sensitive to azoles and peroxide. In order to understand the cellular response to dysfunctional mitochondria, genome-wide expression profiling of fzo1Δ/Δ cells was performed. Our results show that the increased susceptibility to azoles was likely due to reduced efflux activity of CDR efflux pumps, caused by the missorting of Cdr1p into the vacuole. In addition, fzo1Δ/Δ cells showed upregulation of genes involved in iron assimilation, in iron-sufficient conditions, characteristic of iron-starved cells. One of the consequent effects was downregulation of genes of the ergosterol biosynthesis pathway with a commensurate decrease in cellular ergosterol levels. We therefore connect deregulated iron metabolism to ergosterol biosynthesis pathway in response to dysfunctional mitochondria. Impaired activation of the Hog1 pathway in the mutant was the basis for increased susceptibility to peroxide and increase in reactive oxygen species, indicating the importance of functional mitochondria in controlling Hog1-mediated oxidative stress response. Mitochondrial phospholipid levels were also altered as indicated by an increase in phosphatidylserine and phosphatidylethanolamine and decrease in phosphatidylcholine in fzo1Δ/Δ cells. Collectively, these findings reinforce the connection between functional mitochondria and azole tolerance, oxidant-mediated stress, and iron homeostasis in C. albicans.
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