Nonlinear feedback drives homeostatic plasticity in H2O2 stress response

Elife. 2017 Apr 18;6:e23971. doi: 10.7554/eLife.23971.


Homeostatic systems that rely on genetic regulatory networks are intrinsically limited by the transcriptional response time, which may restrict a cell's ability to adapt to unanticipated environmental challenges. To bypass this limitation, cells have evolved mechanisms whereby exposure to mild stress increases their resistance to subsequent threats. However, the mechanisms responsible for such adaptive homeostasis remain largely unknown. Here, we used live-cell imaging and microfluidics to investigate the adaptive response of budding yeast to temporally controlled H2O2 stress patterns. We demonstrate that acquisition of tolerance is a systems-level property resulting from nonlinearity of H2O2 scavenging by peroxiredoxins and our study reveals that this regulatory scheme induces a striking hormetic effect of extracellular H2O2 stress on replicative longevity. Our study thus provides a novel quantitative framework bridging the molecular architecture of a cellular homeostatic system to the emergence of nonintuitive adaptive properties.

Keywords: H2O2 homeostasis; S. cerevisiae; acquired stress resistance; adaptation; cell biology; computational biology; hormesis; nonlinear feedback; systems biology.

MeSH terms

  • Feedback*
  • Hydrogen Peroxide / toxicity*
  • Intravital Microscopy
  • Microfluidics
  • Optical Imaging
  • Oxidants / toxicity*
  • Oxidative Stress*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / physiology*
  • Stress, Physiological*


  • Oxidants
  • Hydrogen Peroxide

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.