Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata

FEMS Yeast Res. 2016 Aug;16(5):fow054. doi: 10.1093/femsyr/fow054. Epub 2016 Jul 1.


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.

Keywords: Candida glabrata; catalase; oxidative stress response; superoxide dismutase; vacuolar H+-ATPase.

MeSH terms

  • Alkalies / toxicity
  • Candida glabrata / enzymology*
  • Candida glabrata / genetics
  • Candida glabrata / metabolism
  • Candida glabrata / physiology*
  • Catalase / metabolism
  • Copper / metabolism*
  • Cytosol / chemistry
  • Gene Deletion
  • Hydrogen Peroxide / toxicity
  • Molecular Chaperones / genetics
  • Oxidative Stress*
  • Proton-Translocating ATPases / metabolism*
  • Reactive Oxygen Species / analysis
  • Superoxide Dismutase / metabolism
  • Vacuoles / enzymology*
  • Vacuoles / metabolism*


  • Alkalies
  • Molecular Chaperones
  • Reactive Oxygen Species
  • Copper
  • Hydrogen Peroxide
  • Catalase
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Proton-Translocating ATPases