Work

Dissecting the functional and spatial roles of peroxiredoxins as H2O2 scavengers and redox transducers

Year: 2026

Type: article

Abstract: Since their discovery in the late 1980s as peroxidases that eliminate hydrogen peroxide (H 2 O 2 ), 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 H 2 O 2 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 H 2 O 2 and activate Pap1 was assessed. Both scavengers can complement the growth defects of cells lacking Tpx1 in high oxygen. Combined with H 2 O 2 biosensors, our results show that Tpx1 efficiently controls H 2 O 2 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.

Source: Cellular and Molecular Life Sciences

DOI: 10.1007/s00018-026-06356-1

Authors: Laura de Cubas, Adrian Konopko, Susanna Boronat, José Ayté, Elena Hidalgo

Institutions: Universitat Pompeu Fabra, German Cancer Research Center, DKFZ-ZMBH Alliance

Language: English

Topic: Redox biology and oxidative stress

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $4,290

Funder: Universitat Pompeu Fabra