title: The mitochondrial protein Mcu1 plays important roles in carbon source utilization, filamentation, and virulence in Candida albicans.
abstract: The fungus Candida albicans is both a pathogen and a commensal in humans. The ability to utilize different carbon sources available in diverse host niches is vital for both commensalism and pathogenicity. N-acetylglucosamine (GlcNAc) is an important signaling molecule as well as a carbon source in C. albicans. Here, we report the discovery of a novel gene MCU1 essential for GlcNAc utilization. Mcu1 is located in mitochondria and associated with multiple energy- and metabolism-related proteins including Por1, Atp1, Pet9, and Mdh1. Consistently, inactivating Por1 impaired GlcNAc utilization as well. Deletion of MCU1 also caused defects in utilizing non-fermentable carbon sources and amino acids. Furthermore, MCU1 is required for filamentation in several inducing conditions and virulence in a mouse systemic infection model. We also deleted TGL99 and GUP1, two genes adjacent to MCU1, and found that the gup1/gup1 mutant exhibited mild defects in the utilization of several carbon sources including GlcNAc, maltose, galactose, amino acids, and ethanol. Our results indicate that MCU1 exists in a cluster of genes involved in the metabolism of carbon sources. Given its importance in metabolism and lack of a homolog in humans, Mcu1 could be a potential target for developing antifungal agents.
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guobo
authors.initials: G
authors.lastname: Guan
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Proteos, Singapore 138673, Singapore.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794-5222, USA.
authors.forename: Shamoon
authors.initials: S
authors.lastname: Naseem
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794-5222, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Konopka
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Proteos, Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 138673, Singapore.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: huanggh@im.ac.cn.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Huang
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002176:Candida albicans / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D058387:Candidemia / Q000382:microbiology; D002244:Carbon / Q000378:metabolism*; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D025301:Hyphae / Q000166:cytology / Q000254:growth & development*; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D014774:Virulence
chemical_list: D000596:Amino Acids; D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D002244:Carbon; D000117:Acetylglucosamine
keywords: Candida albicans; Carbon source utilization; Filamentation; Mcu1; Por1; Virulence