Open AccessFungal‐specific subunits of the C andida albicans mitochondrial complex I drive diverse cell functions including cell wall synthesis
Author(s) -
She Xiaodong,
Khamooshi Kasra,
Gao Yin,
Shen Yongnian,
Lv Yuxia,
Calderone Richard,
Fonzi William,
Liu Weida,
Li Dongmei
Publication year - 2015
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12438
Subject(s) - biology , candida albicans , mutant , protein subunit , gene , nadh dehydrogenase , corpus albicans , mitochondrion , phenotype , biochemistry , microbiology and biotechnology , genetics
Summary Our published research has focused on the role of G oa1p, an apparent regulator of the C andida albicans mitochondrial complex I ( CI ). Lack of Goa1p affects optimum cell growth, CI activity and virulence. Eukaryotic CI is composed of a core of 14 alpha‐proteobacterial subunit proteins and a variable number of supernumerary subunit proteins. Of the latter group of proteins, one ( NUZM ) is fungal specific and the other ( NUXM ) is found in fungi, algae and plants, but is not a mammalian CI subunit protein. We have established that NUXM is orf19.6607 and NUZM is orf19.287 in C . albicans . Herein, we validate both subunit proteins as NADH :ubiquinone oxidoreductases ( NUO ) and annotate their gene functions. To accomplish these objectives, we compared null mutants of each with wild type ( WT ) and gene‐reconstituted strains. Genetic mutants of genes NUO 1 (orf19.6607) and NUO 2 (orf19.287), not surprisingly, each had reduced oxygen consumption, decreased mitochondrial redox potential, decreased CI activity, increased reactive oxidant species ( ROS ) and decreased chronological ageing in vitro . Loss of either gene results in disassembly of CI . Transcriptional profiling of both mutants indicated significant down‐regulation of genes of carbon metabolism, as well as up‐regulation of mitochondrial‐associated gene families that may occur to compensate for the loss of CI activity. Profiling of both mutants also demonstrated a loss of cell wall β‐mannosylation but not in a conserved CI subunit ( ndh51 Δ). The profiling data may indicate specific functions driven by the enzymatic activity of N uo1p and N uo2p. Of importance, each mutant is also avirulent in a murine blood‐borne, invasive model of candidiasis associated with their reduced colonization of tissues. Based on their fungal specificity and roles in virulence, we suggest both as drug targets for antifungal drug discovery.