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However, the molecular mechanism underlying the protective role of V\u2010ATPase 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\u2010ATPase plays a crucial role in pumping excessive cytosolic protons into the vacuole, the metal\u2010sensitive phenotypes of the\n                    <jats:italic>\u0394vma2<\/jats:italic>\n                    and\n                    <jats:italic>\u0394vma3<\/jats:italic>\n                    mutants lacking V\u2010ATPase activity were supposed to result from highly acidified cytosol. However, we found that the metal\u2010sensitive 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\u2010ATPase function led to aberrant vacuolar morphology and defective endocytic trafficking. Furthermore, the sensitivities of the\n                    <jats:italic>\u0394vma<\/jats:italic>\n                    mutants to other chemical compounds (i.e. acetic acid, H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , menadione, tunicamycin and cycloheximide) were a consequence of increased endogenous oxidative stress. These findings, therefore, suggest the important role of V\u2010ATPase in preventing endogenous oxidative stress induced by metals and other chemical compounds.\n                  <\/jats:p>","DOI":"10.1111\/1462-2920.15022","type":"journal-article","created":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T20:49:15Z","timestamp":1586897355000},"page":"2403-2418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Vacuolar H\n                    <sup>+<\/sup>\n                    \u2010\n                    <scp>ATPase<\/scp>\n                    is involved in preventing heavy metal\u2010induced oxidative stress in\n                    <scp>\n                      <i>Saccharomyces cerevisiae<\/i>\n                    <\/scp>"],"prefix":"10.1111","volume":"22","author":[{"given":"Todsapol","family":"Techo","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Science Mahidol University  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