TY  - JOUR
AU  - Zimmermann, Jannik
AU  - Lang, Lukas
AU  - Calabrese, Gaetano
AU  - Laporte, Hugo
AU  - Amponsah, Prince S
AU  - Michalk, Christoph
AU  - Sukmann, Tobias
AU  - Oestreicher, Julian
AU  - Tursch, Anja
AU  - Peker, Esra
AU  - Owusu, Theresa N E
AU  - Weith, Matthias
AU  - Roma, Leticia Prates
AU  - Deponte, Marcel
AU  - Riemer, Jan
AU  - Morgan, Bruce
TI  - Tsa1 is the dominant peroxide scavenger and a source of H2O2-dependent GSSG production in yeast.
JO  - Free radical biology and medicine
VL  - 226
SN  - 0891-5849
CY  - New York, NY [u.a.]
PB  - Elsevier
M1  - DKFZ-2024-02480
SP  - 408 - 420
PY  - 2025
N1  - DKFZ-ZMBH Alliance
AB  - Hydrogen peroxide (H2O2) is an important biological molecule, functioning both as a second messenger in cell signaling and, especially at higher concentrations, as a cause of cell damage. Cells harbor multiple enzymes that have peroxide reducing activity in vitro. However, the contribution of each of these enzymes towards peroxide scavenging in vivo is less clear. Therefore, to directly investigate in vivo peroxide scavenging, we used the genetically encoded peroxide probes, roGFP2-Tsa2ΔCR and HyPer7, to systematically screen the peroxide scavenging capacity of baker's yeast thiol and heme peroxidase mutants. We show that the 2-Cys peroxiredoxin Tsa1 alone is responsible for almost all exogenous H2O2 and tert-butyl hydroperoxide scavenging. Furthermore, Tsa1 can become an important source of H2O2-dependent cytosolic glutathione disulfide production. The two catalases and cytochrome c peroxidase only produce observable scavenging defects at higher H2O2 concentrations when these three heme peroxidases are removed in combination. We also analyzed the reduction of Tsa1 in vitro, revealing that the enzyme is efficiently reduced by thioredoxin-1 with a rate constant of 2.8 × 106 M-1s-1 but not by glutaredoxin-2. Tsa1 reduction by reduced glutathione occurs nonenzymatically with a rate constant of 2.9 M-1s-1. Hence, the observed Tsa1-dependent glutathione disulfide production in yeast probably requires the oxidation of thioredoxins. Our findings clarify the importance of the various thiol and heme peroxidases for peroxide removal and suggest that most thiol peroxidases have alternative or specialized functions in specific subcellular compartments.
KW  - Catalase (Other)
KW  - H(2)O(2) scavenging (Other)
KW  - Heme peroxidase (Other)
KW  - HyPer7 (Other)
KW  - Peroxiredoxin (Other)
KW  - Thiol peroxidase (Other)
KW  - roGFP2 (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39515595
DO  - DOI:10.1016/j.freeradbiomed.2024.11.004
UR  - https://inrepo02.dkfz.de/record/294765
ER  -