Abstract
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.
Highlights
Fungal infection is still an important medical issue worldwide and poses a significant threat to human health [1]
We describe the molecular mechanisms through which mitochondria are involved in regulating azole resistance and fungal pathogenicity and discuss the possibility for targeting mitochondrial factors for the development of antifungal therapies
Because of the connections of mitochondria to azole resistance, lipid metabolism, pathogenesis, and cell wall regulation, pharmacological disruption of mitochondrial function may prove to be effective against fungal pathogens
Summary
Fungal infection is still an important medical issue worldwide and poses a significant threat to human health [1]. There is an urgent need to unravel the molecular mechanisms of azole resistance to search for new and effective therapies. Azole drug resistance and the fungal virulence are intimately intertwined with their metabolism, and mitochondria play a central role in that metabolism [12,13]. Mitochondria house and integrate multiple metabolic functions relating to lipids, iron metabolism, energy production, and cell wall biosynthesis [14,15,16,17,18,19], which are associated with fungal virulence and resistance to azoles. We describe the molecular mechanisms through which mitochondria are involved in regulating azole resistance and fungal pathogenicity and discuss the possibility for targeting mitochondrial factors for the development of antifungal therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
