Hyperoxidation of mitochondrial peroxiredoxin limits H2O2‐induced cell death in yeast

• Gaetano Calabrese ^[1] ; Esra Peker ^[1] ; Prince Saforo Amponsah ^[3] ; Michaela Nicole Hoehne ^[1] ; Trine Riemer ^[1] ; Marie Mai ^[4] ; Gerd Patrick Bienert ^[5] ; Marcel Deponte ^[2] ; Bruce Morgan ^[4] ; Jan Riemer ^[1]
  1. [1] University of Cologne

     University of Cologne

     Kreisfreie Stadt Köln, Alemania

     
  2. [2] University of Kaiserslautern

     University of Kaiserslautern

     Kreisfreie Stadt Kaiserslautern, Alemania

     
  3. [3] 2 Department for Biology Cellular Biochemistry University of Kaiserslautern Kaiserslautern Germany; 3 Institute of Biochemistry University of the Saarland Saarbruecken Germany
  4. [4] 3 Institute of Biochemistry University of the Saarland Saarbruecken Germany
  5. [5] 4 Department of Physiology and Cell Biology Leibniz‐Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben Germany

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 38, Nº. 18, 2019
• Idioma: inglés
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  • Hydrogen peroxide (H2O2) plays important roles in cellular signaling, yet nonetheless is toxic at higher concentrations. Surprisingly, the mechanism(s) of cellular H2O2 toxicity remain poorly understood. Here, we reveal an important role for mitochondrial 1‐Cys peroxiredoxin from budding yeast, Prx1, in regulating H2O2‐induced cell death. We show that Prx1 efficiently transfers oxidative equivalents from H2O2 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 H2O2 challenge. By replacing PRX1 with natural and engineered peroxiredoxin variants, we could predictably induce widely differing matrix glutathione responses to H2O2. Therefore, we demonstrated a key role for matrix glutathione oxidation in driving H2O2‐induced cell death. Finally, we reveal that hyperoxidation of Prx1 serves as a switch‐off mechanism to limit oxidation of matrix glutathione at high H2O2 concentrations. This enables yeast cells to strike a fine balance between H2O2 removal and limitation of matrix glutathione oxidation.