Unique, Diverged, and Conserved Mitochondrial Functions Influencing Candida albicans Respiration

• Published in: mBio Vol. 10; no. 3
• Main Authors: Sun, Nuo, Parrish, Rebecca S, Calderone, Richard A, Fonzi, William A
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 25.06.2019
• Subjects: Candida albicans - genetics; Candida albicans - metabolism; Electron Transport Complex I - genetics; evolution; fungi; Gene Deletion; Gene Expression Regulation, Fungal; Genes, Fungal; mitochondria; Mitochondria - metabolism; Mitochondrial Proteins - genetics; Molecular Biology and Physiology; pathogens; Virulence - genetics; evolution; pathogens; fungi; mitochondria
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mbio.00300-19

is an opportunistic fungal pathogen of major clinical concern. The virulence of this pathogen is intimately intertwined with its metabolism. Mitochondria, which have a central metabolic role, have undergone many lineage-specific adaptations in association with their eukaryotic host. A screen for lineage-specific genes identified seven such genes specific to the CTG clade of fungi, of which is a member. Each is required for respiratory growth and is integral to expression of complex I, III, or IV of the electron transport chain. Two genes, and , encode supernumerary subunits of complex I, whereas and have nonstructural roles in expression of complex I. Similarly, the other three genes have nonstructural roles in expression of complex III ( ) or complex IV ( and ). In addition to these novel additions, an alternative functional assignment was found for the mitochondrial protein encoded by was required for complex I expression in , whereas the distantly related ortholog participates in expression of complex III. Phenotypic analysis of deletion mutants showed that fermentative metabolism is unable to support optimal growth rates or yields of However, yeast-hypha morphogenesis, an important virulence attribute, did not require respiratory metabolism under hypoxic conditions. The inability to respire also resulted in hypersensitivity to the antifungal fluconazole and in attenuated virulence in a infection model. The results show that lineage-specific adaptations have occurred in mitochondria and highlight the significance of respiratory metabolism in the pathobiology of is an opportunistic fungal pathogen of major clinical concern. The virulence of this pathogen is intimately intertwined with its metabolic behavior, and mitochondria have a central role in that metabolism. Mitochondria have undergone many evolutionary changes, which include lineage-specific adaptations in association with their eukaryotic host. Seven lineage-specific genes required for electron transport chain function were identified in the CTG clade of fungi, of which is a member. Additionally, examination of several highly diverged orthologs encoding mitochondrial proteins demonstrated functional reassignment for one of these. Deficits imparted by deletion of these genes revealed the critical role of respiration in virulence attributes of the fungus and highlight important evolutionary adaptations in metabolism.