title: Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata.
abstract: Vacuolar H(+)-ATPase (V-ATPase) is responsible for the acidification of eukaryotic intracellular compartments and plays an important role in oxidative stress response (OSR), but its molecular bases are largely unknown. Here, we investigated how V-ATPase is involved in the OSR by using a strain lacking VPH2, which encodes an assembly factor of V-ATPase, in the pathogenic fungus Candida glabrata The loss of Vph2 resulted in increased H2O2 sensitivity and intracellular reactive oxygen species (ROS) level independently of mitochondrial functions. The Δvph2 mutant also displayed growth defects under alkaline conditions accompanied by the accumulation of intracellular ROS and these phenotypes were recovered in the presence of the ROS scavenger N-acetyl-l-cysteine. Both expression and activity levels of mitochondrial manganese superoxide dismutase (Sod2) and catalase (Cta1) were decreased in the Δvph2 mutant. Phenotypic analyses of strains lacking and overexpressing these genes revealed that Sod2 and Cta1 play a predominant role in endogenous and exogenous OSR, respectively. Furthermore, supplementation of copper and iron restored the expression of SOD2 specifically in the Δvph2 mutant, suggesting that the homeostasis of intracellular cupper and iron levels maintained by V-ATPase was important for the Sod2-mediated OSR. This report demonstrates novel roles of V-ATPase in the OSR in C. glabrata.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan Division of Infectious Diseases, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan taiga-m@nagasaki-u.ac.jp.
authors.forename: Taiga
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Sciences, Suzuka, Mie 513-8670, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Minematsu
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamauchi
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan Division of Infectious Diseases, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takazono
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Shimamura
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Division of Infectious Diseases, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Izumikawa
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.affiliation: Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
mesh_terms: D000468:Alkalies / Q000633:toxicity; D041221:Candida glabrata / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry; D017353:Gene Deletion; D006861:Hydrogen Peroxide / Q000633:toxicity; D018832:Molecular Chaperones / Q000235:genetics; D018384:Oxidative Stress; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis; D013482:Superoxide Dismutase / Q000378:metabolism; D014617:Vacuoles / Q000201:enzymology* / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D000468:Alkalies; D002374:Catalase; D003300:Copper; D006861:Hydrogen Peroxide; D018832:Molecular Chaperones; D006180:Proton-Translocating ATPases; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
keywords: Candida glabrata; catalase; oxidative stress response; superoxide dismutase; vacuolar H+-ATPase