Superoxide radicals have a protective role during H2O2 stress

Mol Biol Cell. 2013 Sep;24(18):2876-84. doi: 10.1091/mbc.E13-01-0052. Epub 2013 Jul 17.

Abstract

Reactive oxygen species (ROS) consist of potentially toxic, partly reduced oxygen species and free radicals. After H(2)O(2) treatment, yeast cells significantly increase superoxide radical production. Respiratory chain complex III and possibly cytochrome b function are essential for this increase. Disruption of complex III renders cells sensitive to H(2)O(2) but not to the superoxide radical generator menadione. Of interest, the same H(2)O(2)-sensitive mutant strains have the lowest superoxide radical levels, and strains with the highest resistance to H(2)O(2) have the highest levels of superoxide radicals. Consistent with this correlation, overexpression of superoxide dismutase increases sensitivity to H(2)O(2), and this phenotype is partially rescued by addition of small concentrations of menadione. Small increases in levels of mitochondrially produced superoxide radicals have a protective effect during H(2)O(2)-induced stress, and in response to H(2)O(2), the wild-type strain increases superoxide radical production to activate this defense mechanism. This provides a direct link between complex III as the main source of ROS and its role in defense against ROS. High levels of the superoxide radical are still toxic. These opposing, concentration-dependent roles of the superoxide radical comprise a form of hormesis and show one ROS having a hormetic effect on the toxicity of another.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / drug effects
  • Cytochromes b / metabolism
  • Cytoprotection / drug effects*
  • Electron Transport / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hydrogen Peroxide / toxicity*
  • Microbial Viability / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mutation / genetics
  • Oxidative Stress / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism
  • Stress, Physiological / drug effects*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxides / pharmacology*

Substances

  • RNA, Messenger
  • Superoxides
  • Cytochromes b
  • Hydrogen Peroxide
  • Superoxide Dismutase