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. 2025 Mar 20;32(3):511-519.e5.
doi: 10.1016/j.chembiol.2025.01.009. Epub 2025 Feb 25.

Dynamic PRDX S-acylation modulates ROS stress and signaling

Tian Qiu  1 , Saara-Anne Azizi  2 , Shubhashree Pani  1 , Bryan C Dickinson  3
Affiliations

Dynamic PRDX S-acylation modulates ROS stress and signaling

Tian Qiu et al. Cell Chem Biol. .

Abstract

Peroxiredoxins (PRDXs) are a highly conserved family of peroxidases that serve as the primary scavengers of peroxides. Post-translational modifications play crucial roles modulating PRDX activities, tuning the balance between reactive oxygen species (ROS) signaling and stress. We previously reported that S-acylation occurs at the "peroxidatic" cysteine (Cp) site of PRDX5 and that it inhibits PRDX5 activity. Here, we show that the PRDX family more broadly is subject to S-acylation at the Cp site of all PRDXs and that PRDX S-acylation dynamically responds to cellular ROS levels. Using activity-based fluorescent imaging with DPP-Red, a red-shifted fluorescent indicator for acyl-protein thioesterase (APT) activity, we also discover that the instigation of ROS-stress via exogenous H2O2 activates both the cytosolic and mitochondrial APTs, whereas epidermal growth factor (EGF)-stimulated endogenous H2O2 deactivates the cytosolic APTs. These results indicate that APTs help tune H2O2 signal transduction and ROS protection through PRDX S-deacylation.

Keywords: PRDX peroxiredoxin; ROS; S-palmitoylation; fluorescent probe; hydrogen peroxide; protein lipidation.

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Conflict of interest statement

Declaration of interests B.C.D. has a patent on the DPP technology used in this work.

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