A trade-off between stress resistance and tolerance underlies the adaptive response to hydrogen peroxide

Abstract

AbstractIn response to environmental stress, cellular defense strategies may be divided into two categories: those, as in homeostatic systems, that seek to maintain cell proliferation by degrading the stressor (i.e., resistance); and those that ensure cell survival (i.e. tolerance), even if this is often at the expense of cell proliferation. In this study, we have explored the genetic bases of the antagonism between resistance and tolerance during the response to hydrogen peroxide (H2O2) in budding yeast. We show that inactivation of protein kinase A (PKA) by H2O2 signaling induces an abrupt transition from normal homeostatic function to a stress-tolerant state by protecting the growth machinery, hence maximizing cellular fitness in a changing environment. This model system paves the way for developing antiproliferative strategies that target both resistance and tolerance mechanisms to prevent relapse.