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Hyperoxidation of mitochondrial peroxiredoxin limits H 2 O 2 ‐induced cell death in yeast
Author(s) -
Calabrese Gaetano,
Peker Esra,
Amponsah Prince Saforo,
Hoehne Michaela Nicole,
Riemer Trine,
Mai Marie,
Bienert Gerd Patrick,
Deponte Marcel,
Morgan Bruce,
Riemer Jan
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019101552
Subject(s) - biology , yeast , mitochondrion , programmed cell death , saccharomyces cerevisiae , peroxiredoxin , mitochondrial dna , genetics , microbiology and biotechnology , enzyme , biochemistry , gene , apoptosis , peroxidase
Hydrogen peroxide (H 2 O 2 ) plays important roles in cellular signaling, yet nonetheless is toxic at higher concentrations. Surprisingly, the mechanism(s) of cellular H 2 O 2 toxicity remain poorly understood. Here, we reveal an important role for mitochondrial 1‐Cys peroxiredoxin from budding yeast, Prx1, in regulating H 2 O 2 ‐induced cell death. We show that Prx1 efficiently transfers oxidative equivalents from H 2 O 2 to the mitochondrial glutathione pool. Deletion of PRX 1 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 H 2 O 2 challenge. By replacing PRX 1 with natural and engineered peroxiredoxin variants, we could predictably induce widely differing matrix glutathione responses to H 2 O 2 . Therefore, we demonstrated a key role for matrix glutathione oxidation in driving H 2 O 2 ‐induced cell death. Finally, we reveal that hyperoxidation of Prx1 serves as a switch‐off mechanism to limit oxidation of matrix glutathione at high H 2 O 2 concentrations. This enables yeast cells to strike a fine balance between H 2 O 2 removal and limitation of matrix glutathione oxidation.