Calabrese, Gaetano ORCID: 0000-0002-2212-5280, Peker, Esra, Amponsah, Prince Saforo, Hoehne, Michaela Nicole, Riemer, Trine, Mai, Marie ORCID: 0000-0003-1907-7852, Bienert, Gerd Patrick, Deponte, Marcel ORCID: 0000-0003-2141-917X, Morgan, Bruce ORCID: 0000-0001-9393-1071 and Riemer, Jan . Hyperoxidation of mitochondrial peroxiredoxin limits H2O2-induced cell death in yeast. Embo J.. HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Calabrese, GaetanoUNSPECIFIEDorcid.org/0000-0002-2212-5280UNSPECIFIED
Peker, EsraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amponsah, Prince SaforoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoehne, Michaela NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riemer, TrineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mai, MarieUNSPECIFIEDorcid.org/0000-0003-1907-7852UNSPECIFIED
Bienert, Gerd PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deponte, MarcelUNSPECIFIEDorcid.org/0000-0003-2141-917XUNSPECIFIED
Morgan, BruceUNSPECIFIEDorcid.org/0000-0001-9393-1071UNSPECIFIED
Riemer, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-144663
DOI: 10.15252/embj.2019101552
Journal or Publication Title: Embo J.
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1460-2075
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REDOX-SENSITIVE GFP; HYDROGEN-PEROXIDE; SACCHAROMYCES-CEREVISIAE; 2-CYS PEROXIREDOXIN; 1-CYS PEROXIREDOXIN; GLUTATHIONE DISULFIDE; THIOL PEROXIDASE; PLASMA-MEMBRANE; H2O2; ANTIOXIDANTMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14466

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