Unique, Diverged, and Conserved Mitochondrial Functions Influencing <named-content content-type="genus-species">Candida albicans</named-content> Respiration

ABSTRACT Candida albicans 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 eukaryo...

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Autores principales:	Nuo Sun, Rebecca S. Parrish, Richard A. Calderone, William A. Fonzi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	fungi evolution mitochondria pathogens Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b483d5a66b3648e9b1f9a0b921602610
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spelling	oai:doaj.org-article:b483d5a66b3648e9b1f9a0b9216026102021-11-15T15:55:25ZUnique, Diverged, and Conserved Mitochondrial Functions Influencing <named-content content-type="genus-species">Candida albicans</named-content> Respiration10.1128/mBio.00300-192150-7511https://doaj.org/article/b483d5a66b3648e9b1f9a0b9216026102019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00300-19https://doaj.org/toc/2150-7511ABSTRACT Candida albicans 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 C. albicans 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, NUO3 and NUO4, encode supernumerary subunits of complex I, whereas NUE1 and NUE2 have nonstructural roles in expression of complex I. Similarly, the other three genes have nonstructural roles in expression of complex III (QCE1) or complex IV (COE1 and COE2). In addition to these novel additions, an alternative functional assignment was found for the mitochondrial protein encoded by MNE1. MNE1 was required for complex I expression in C. albicans, whereas the distantly related Saccharomyces cerevisiae 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 C. albicans. 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 Galleria mellonella infection model. The results show that lineage-specific adaptations have occurred in C. albicans mitochondria and highlight the significance of respiratory metabolism in the pathobiology of C. albicans. IMPORTANCE Candida albicans 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 C. albicans 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 C. albicans metabolism.Nuo SunRebecca S. ParrishRichard A. CalderoneWilliam A. FonziAmerican Society for MicrobiologyarticlefungievolutionmitochondriapathogensMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	fungi evolution mitochondria pathogens Microbiology QR1-502
spellingShingle	fungi evolution mitochondria pathogens Microbiology QR1-502 Nuo Sun Rebecca S. Parrish Richard A. Calderone William A. Fonzi Unique, Diverged, and Conserved Mitochondrial Functions Influencing <named-content content-type="genus-species">Candida albicans</named-content> Respiration
description	ABSTRACT Candida albicans 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 C. albicans 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, NUO3 and NUO4, encode supernumerary subunits of complex I, whereas NUE1 and NUE2 have nonstructural roles in expression of complex I. Similarly, the other three genes have nonstructural roles in expression of complex III (QCE1) or complex IV (COE1 and COE2). In addition to these novel additions, an alternative functional assignment was found for the mitochondrial protein encoded by MNE1. MNE1 was required for complex I expression in C. albicans, whereas the distantly related Saccharomyces cerevisiae 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 C. albicans. 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 Galleria mellonella infection model. The results show that lineage-specific adaptations have occurred in C. albicans mitochondria and highlight the significance of respiratory metabolism in the pathobiology of C. albicans. IMPORTANCE Candida albicans 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 C. albicans 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 C. albicans metabolism.
format	article
author	Nuo Sun Rebecca S. Parrish Richard A. Calderone William A. Fonzi
author_facet	Nuo Sun Rebecca S. Parrish Richard A. Calderone William A. Fonzi
author_sort	Nuo Sun
title	Unique, Diverged, and Conserved Mitochondrial Functions Influencing <named-content content-type="genus-species">Candida albicans</named-content> Respiration
title_short	Unique, Diverged, and Conserved Mitochondrial Functions Influencing <named-content content-type="genus-species">Candida albicans</named-content> Respiration
title_full	Unique, Diverged, and Conserved Mitochondrial Functions Influencing <named-content content-type="genus-species">Candida albicans</named-content> Respiration
title_fullStr	Unique, Diverged, and Conserved Mitochondrial Functions Influencing <named-content content-type="genus-species">Candida albicans</named-content> Respiration
title_full_unstemmed	Unique, Diverged, and Conserved Mitochondrial Functions Influencing <named-content content-type="genus-species">Candida albicans</named-content> Respiration
title_sort	unique, diverged, and conserved mitochondrial functions influencing <named-content content-type="genus-species">candida albicans</named-content> respiration
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b483d5a66b3648e9b1f9a0b921602610
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Unique, Diverged, and Conserved Mitochondrial Functions Influencing <named-content content-type="genus-species">Candida albicans</named-content> Respiration

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