Vacuolar H(+) -ATPase is involved in preventing heavy metal-induced oxidative stress in Saccharomyces cerevisiae.
2020
In Saccharomyces cerevisiae, vacuolar H(+) -ATPase (V-ATPase) involved in the regulation of intracellular pH homeostasis has been shown to be important for tolerances to cadmium, cobalt, and nickel. However, molecular mechanism underlying the protective role of V-ATPase against these metals remains unclear. In this study, we show that cadmium, cobalt, and nickel disturbed intracellular pH balance by triggering cytosolic acidification and vacuolar alkalinization, likely via their membrane permeabilizing effects. Since V-ATPase plays a crucial role in pumping excessive cytosolic protons into the vacuole, the metal-sensitive phenotypes of the Deltavma2 and Deltavma3 mutants lacking V-ATPase activity were supposed to result from highly acidified cytosol. However, we found that the metal-sensitive phenotypes of these mutants were caused by increased production of reactive oxygen species, likely as a result of decreased expression and activities of manganese superoxide dismutase and catalase. In addition, the loss of V-ATPase function led to aberrant vacuolar morphology and defective endocytic trafficking. Furthermore, the sensitivities of the Deltavma mutants to other chemical compounds (i.e., acetic acid, H2 O2 , menadione, tunicamycin, and cycloheximide) were a consequence of increased endogenous oxidative stress. These findings therefore suggest the important role of V-ATPase in preventing endogenous oxidative stress induced by metals and other chemical compounds. This article is protected by copyright. All rights reserved.
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