# Moonlighting Functions of Mammalian Peroxiredoxins in Cellular Signaling

## TL;DR

This review explores how mammalian peroxiredoxins (Prdxs) have roles beyond being antioxidants, including sensing peroxides, regulating redox signaling, and acting as molecular chaperones.

## Contribution

The paper highlights the diverse post-translational modifications and isoform-specific functions of Prdxs, emphasizing their roles in cellular signaling and disease.

## Key findings

- Prdxs act as peroxide sensors and modulators of redox signaling through reversible hyperoxidation.
- Prdx isoforms have distinct subcellular localizations and functions in physiological and pathological processes.
- Post-translational modifications regulate Prdx activity and influence cellular signaling.

## Abstract

Peroxiredoxins (Prdxs) are a family of thiol-specific peroxidases that play a central role in maintaining intracellular redox homeostasis. In addition to their classical antioxidant activities, Prdxs function as peroxide sensors, modulators of redox signaling, and molecular chaperones. In this review, we summarize the peroxide-reducing activity, their redox-switch mechanism driven by reversible hyperoxidation, and the chaperone function that arises through oligomerization and accompanying structural changes. We also highlight that the Prdx1–Prdx6 isoforms exhibit distinct subcellular localizations and perform isoform-specific functions, thereby contributing to a wide range of physiological and pathological processes. Furthermore, we compile recent findings showing that diverse post-translational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, glutathionylation, sumoylation, and S-nitrosylation, not only regulate Prdx activity but also contribute to cellular signaling processes. Overall, this review emphasizes that Prdxs are more than simple antioxidant enzymes: they serve as guardians of cellular redox balance and dynamic regulators of signaling networks, underscoring their potential as disease biomarkers and therapeutic targets.