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


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.

SUBMITTER: Calabrese G 

PROVIDER: S-EPMC6745495 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Hyperoxidation of mitochondrial peroxiredoxin limits H<sub>2</sub> O<sub>2</sub> -induced cell death in yeast.

Calabrese Gaetano G   Peker Esra E   Amponsah Prince Saforo PS   Hoehne Michaela Nicole MN   Riemer Trine T   Mai Marie M   Bienert Gerd Patrick GP   Deponte Marcel M   Morgan Bruce B   Riemer Jan J  

The EMBO journal 20190807 18


Hydrogen peroxide (H<sub>2</sub> O<sub>2</sub> ) plays important roles in cellular signaling, yet nonetheless is toxic at higher concentrations. Surprisingly, the mechanism(s) of cellular H<sub>2</sub> O<sub>2</sub> toxicity remain poorly understood. Here, we reveal an important role for mitochondrial 1-Cys peroxiredoxin from budding yeast, Prx1, in regulating H<sub>2</sub> O<sub>2</sub> -induced cell death. We show that Prx1 efficiently transfers oxidative equivalents from H<sub>2</sub> O<sub>2  ...[more]

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