TY - JOUR

T1 - Superoxide radicals have a protective role during H2O2 stress

AU - Thorpe, Geoffrey W

AU - Reodica, Mayfebelle

AU - Davies, Michael Jonathan

AU - Heeren, Gino

AU - Jarolim, Stefanie

AU - Pillay, Bethany

AU - Breitenbach, Michael

AU - Higgins, Vincent J

AU - Dawes, Ian W

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - Adaptation, Physiological

KW - Cytochromes b

KW - Cytoprotection

KW - Electron Transport

KW - Gene Expression Regulation, Enzymologic

KW - Hydrogen Peroxide

KW - Microbial Viability

KW - Mitochondria

KW - Mutation

KW - Oxidative Stress

KW - RNA, Messenger

KW - Saccharomyces cerevisiae

KW - Stress, Physiological

KW - Superoxide Dismutase

KW - Superoxides

U2 - 10.1091/mbc.E13-01-0052

DO - 10.1091/mbc.E13-01-0052

M3 - Journal article

C2 - 23864711

VL - 24

SP - 2876

EP - 2884

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 18

ER -