Dissecting the functional and spatial roles of peroxiredoxins as H₂O₂ scavengers and redox transducers.
- 1Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C/Dr. Aiguader 88, Barcelona, 08003, Spain.
- 2Division of Redox Regulation, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Heidelberg, 69120, Germany.
- 3Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C/Dr. Aiguader 88, Barcelona, 08003, Spain. [email protected].
Abstract
Since their discovery in the late 1980s as peroxidases that eliminate hydrogen peroxide (H₂O₂), peroxiredoxins (Prxs) have been recognized not only for detoxification but also for roles in redox signaling. In fission yeast, the main Prx, Tpx1, maintains steady-state H₂O₂ below toxic levels through its scavenging activity. Under excess peroxides, Tpx1 switches to a signaling role, transmitting oxidative signals to the transcription factor Pap1. Dissecting the relative contributions of Tpx1's peroxidase and sensor functions is challenging. To address this, we used a synthetic biology strategy to separate these dual roles. Tpx1 or catalase (Ctt1) was expressed in distinct subcellular compartments, and their capacity to remove H₂O₂ and activate Pap1 was assessed. Both scavengers can complement the growth defects of cells lacking Tpx1 in high oxygen. Combined with H₂O₂ biosensors, our results show that Tpx1 efficiently controls H₂O₂ levels from any compartment, whereas Ctt1 does not. However, cells expressing mitochondrial- or nuclear-targeted Tpx1 display reduced oxidative stress tolerance because Pap1 activation requires cytosolic Tpx1. Overall, Tpx1 is a highly effective peroxidase throughout the cell, but its subcellular localization is essential for proper redox signaling regulation.
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BibTeX
@article{cubas2026dissecting,
title = {{Dissecting the functional and spatial roles of peroxiredoxins as H₂O₂ scavengers and redox transducers.}},
author = {Laura de Cubas and Adrian Konopko and Susanna Boronat and José Ayté and Elena Hidalgo},
journal = {Cellular and molecular life sciences : CMLS},
year = {2026},
month = jul,
doi = {10.1007/s00018-026-06356-1},
url = {https://europepmc.org/article/MED/42897284},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dissecting the functional and spatial roles of peroxiredoxins as H₂O₂ scavengers and redox transducers.
AU - Laura de Cubas
AU - Adrian Konopko
AU - Susanna Boronat
AU - José Ayté
AU - Elena Hidalgo
PY - 2026
DA - 2026/07/01
JO - Cellular and molecular life sciences : CMLS
DO - 10.1007/s00018-026-06356-1
UR - https://europepmc.org/article/MED/42897284
AB - Since their discovery in the late 1980s as peroxidases that eliminate hydrogen peroxide (H₂O₂), peroxiredoxins (Prxs) have been recognized not only for detoxification but also for roles in redox signaling. In fission yeast, the main Prx, Tpx1, maintains steady-state H₂O₂ below toxic levels through its scavenging activity. Under excess peroxides, Tpx1 switches to a signaling role, transmitting oxidative signals to the transcription factor Pap1. Dissecting the relative contributions of Tpx1's peroxidase and sensor functions is challenging. To address this, we used a synthetic biology strategy to separate these dual roles. Tpx1 or catalase (Ctt1) was expressed in distinct subcellular compartments, and their capacity to remove H₂O₂ and activate Pap1 was assessed. Both scavengers can complement the growth defects of cells lacking Tpx1 in high oxygen. Combined with H₂O₂ biosensors, our results show that Tpx1 efficiently controls H₂O₂ levels from any compartment, whereas Ctt1 does not. However, cells expressing mitochondrial- or nuclear-targeted Tpx1 display reduced oxidative stress tolerance because Pap1 activation requires cytosolic Tpx1. Overall, Tpx1 is a highly effective peroxidase throughout the cell, but its subcellular localization is essential for proper redox signaling regulation.
SN - 1420-682X
SN - 1420-9071
ER -