Abstract:
Hydrogen peroxide is thought to regulate cellular processes by
direct oxidation of numerous cellular proteins, whereas antioxidants,
most notably thiol peroxidases, are thought to reduce
peroxides and inhibit H2O2 response. However, thiol peroxidases
have also been implicated in activation of transcription factors
and signaling. It remains unclear if these enzymes stimulate or
inhibit redox regulation and whether this regulation is widespread
or limited to a few cellular components. Herein, we found that
Saccharomyces cerevisiae cells lacking all eight thiol peroxidases
were viable and withstood redox stresses. They transcriptionally
responded to various redox treatments, but were unable to activate
and repress gene expression in response to H2O2. Further
studies involving redox transcription factors suggested that thiol
peroxidases are major regulators of global gene expression in
response to H2O2. The data suggest that thiol peroxidases sense
and transfer oxidative signals to the signaling proteins and regulate
transcription, whereas a direct interaction between H2O2 and
other cellular proteins plays a secondary role.
