Hyperoxidation of mitochondrial peroxiredoxin limits H2 O2 -induced cell death in yeast

The EMBO Journal
Gaetano CalabreseJan Riemer

Abstract

Hydrogen peroxide (H2 O2 ) plays important roles in cellular signaling, yet nonetheless is toxic at higher concentrations. Surprisingly, the mechanism(s) of cellular H2 O2 toxicity remain poorly understood. Here, we reveal an important role for mitochondrial 1-Cys peroxiredoxin from budding yeast, Prx1, in regulating H2 O2 -induced cell death. We show that Prx1 efficiently transfers oxidative equivalents from H2 O2 to the mitochondrial glutathione pool. Deletion of PRX1 abrogates glutathione oxidation and leads to a cytosolic adaptive response involving upregulation of the catalase, Ctt1. Both of these effects contribute to improved cell viability following an acute H2 O2 challenge. By replacing PRX1 with natural and engineered peroxiredoxin variants, we could predictably induce widely differing matrix glutathione responses to H2 O2 . Therefore, we demonstrated a key role for matrix glutathione oxidation in driving H2 O2 -induced cell death. Finally, we reveal that hyperoxidation of Prx1 serves as a switch-off mechanism to limit oxidation of matrix glutathione at high H2 O2 concentrations. This enables yeast cells to strike a fine balance between H2 O2 removal and limitation of matrix glutathione oxidation.

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Citations

Mar 18, 2020·Plant Signaling & Behavior·Heng ZhouYanjie Xie
Nov 5, 2020·International Journal of Molecular Sciences·Alexander I KostyukDmitry S Bilan
Nov 30, 2020·Free Radical Biology & Medicine·Eloisa Aparecida Vilas-BoasLeticia Prates Roma
Feb 13, 2021·Nature Chemical Biology·Prince Saforo AmponsahBruce Morgan
Apr 11, 2020·Developmental Cell·Sasha De HenauTobias B Dansen
Aug 18, 2020·Biochimica Et Biophysica Acta. General Subjects·Chang-Cheng LiRui Bao
Jun 27, 2021·The FEBS Journal·Daria D SmolyarovaVsevolod V Belousov
Aug 12, 2021·Redox Report : Communications in Free Radical Research·Ché S Pillay, Nolyn John
Oct 8, 2021·Free Radical Biology & Medicine·Shani DoronShilo Rosenwasser

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Methods Mentioned

BETA
environmental stresses
PCR

Software Mentioned

DESeq2
ImageJ
Gorilla
HISAT2
OriginLab
Galaxy

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