Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development
In recent years, the role of mitochondria in pathogenic fungi in terms of azole resistance and fungal pathogenicity has been a rapidly developing field. In this review, we describe the molecular mechanisms by which mitochondria are involved in regulating azole resistance and fungal pathogenicity. Mi...
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| Format: | Article |
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MDPI AG
2020-10-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/10/1574 |
| _version_ | 1797551145425567744 |
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| author | Jinxing Song Jingwen Zhou Lei Zhang Rongpeng Li |
| author_facet | Jinxing Song Jingwen Zhou Lei Zhang Rongpeng Li |
| author_sort | Jinxing Song |
| collection | DOAJ |
| description | In recent years, the role of mitochondria in pathogenic fungi in terms of azole resistance and fungal pathogenicity has been a rapidly developing field. In this review, we describe the molecular mechanisms by which mitochondria are involved in regulating azole resistance and fungal pathogenicity. Mitochondrial function is involved in the regulation of drug efflux pumps at the transcriptional and posttranslational levels. On the one hand, defects in mitochondrial function can serve as the signal leading to activation of calcium signaling and the pleiotropic drug resistance pathway and, therefore, can globally upregulate the expression of drug efflux pump genes, leading to azole drug resistance. On the other hand, mitochondria also contribute to azole resistance through modulation of drug efflux pump localization and activity. Mitochondria further contribute to azole resistance through participating in iron homeostasis and lipid biosynthesis. Additionally, mitochondrial dynamics play an important role in azole resistance. Meanwhile, mitochondrial morphology is important for fungal virulence, playing roles in growth in stressful conditions in a host. Furthermore, there is a close link between mitochondrial respiration and fungal virulence, and mitochondrial respiration plays an important role in morphogenetic transition, hypoxia adaptation, and cell wall biosynthesis. Finally, we discuss the possibility for targeting mitochondrial factors for the development of antifungal therapies. |
| first_indexed | 2024-03-10T15:40:34Z |
| format | Article |
| id | doaj.art-82cf37097af34fabae111aba8efb778c |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T15:40:34Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-82cf37097af34fabae111aba8efb778c2023-11-20T16:51:42ZengMDPI AGMicroorganisms2076-26072020-10-01810157410.3390/microorganisms8101574Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic DevelopmentJinxing Song0Jingwen Zhou1Lei Zhang2Rongpeng Li3The Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province and School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, ChinaThe Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province and School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, ChinaShandong Provincial Key Laboratory of Infection and Immunity, Jinan 250012, ChinaThe Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province and School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, ChinaIn recent years, the role of mitochondria in pathogenic fungi in terms of azole resistance and fungal pathogenicity has been a rapidly developing field. In this review, we describe the molecular mechanisms by which mitochondria are involved in regulating azole resistance and fungal pathogenicity. Mitochondrial function is involved in the regulation of drug efflux pumps at the transcriptional and posttranslational levels. On the one hand, defects in mitochondrial function can serve as the signal leading to activation of calcium signaling and the pleiotropic drug resistance pathway and, therefore, can globally upregulate the expression of drug efflux pump genes, leading to azole drug resistance. On the other hand, mitochondria also contribute to azole resistance through modulation of drug efflux pump localization and activity. Mitochondria further contribute to azole resistance through participating in iron homeostasis and lipid biosynthesis. Additionally, mitochondrial dynamics play an important role in azole resistance. Meanwhile, mitochondrial morphology is important for fungal virulence, playing roles in growth in stressful conditions in a host. Furthermore, there is a close link between mitochondrial respiration and fungal virulence, and mitochondrial respiration plays an important role in morphogenetic transition, hypoxia adaptation, and cell wall biosynthesis. Finally, we discuss the possibility for targeting mitochondrial factors for the development of antifungal therapies.https://www.mdpi.com/2076-2607/8/10/1574azole resistancepathogenic fungimitochondriacalcium signaling |
| spellingShingle | Jinxing Song Jingwen Zhou Lei Zhang Rongpeng Li Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development Microorganisms azole resistance pathogenic fungi mitochondria calcium signaling |
| title | Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development |
| title_full | Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development |
| title_fullStr | Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development |
| title_full_unstemmed | Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development |
| title_short | Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development |
| title_sort | mitochondria mediated azole drug resistance and fungal pathogenicity opportunities for therapeutic development |
| topic | azole resistance pathogenic fungi mitochondria calcium signaling |
| url | https://www.mdpi.com/2076-2607/8/10/1574 |
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