Heterooligomerization drives structural plasticity of eukaryotic peroxiredoxins

Zimmermann, J.; Lang, L.; Malo Pueyo, J.; Reidel, M.; Wahni, K.; Stobbe, D.; Lux, C.; Janvier, S.; Vertommen, D.; Lenhard, S.; Hannemann, F.; Castro, H.; Tomas, A. M.; Herrmann, J.; Salvador, A.; Muehlhaus, T.; Riemer, J.; Messens, J.; Deponte, M.; Morgan, B.

doi:10.1101/2025.03.03.641172

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bioRxiv · 10.1101/2025.03.03.641172

Heterooligomerization drives structural plasticity of eukaryotic peroxiredoxins

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Abstract

Peroxiredoxins are highly conserved thiol peroxidases essential for peroxide detoxification, redox signaling, and chaperone activity. Prx1/AhpC-type peroxiredoxins are found throughout the eukaryotic kingdom, where multiple isoforms frequently coexist within the same cell and even in the same subcellular compartment. Long thought to form exclusively homooligomeric structures, we reveal that heterooligomerization is a conserved and important feature of eukaryotic Prx1/AhpC-type peroxiredoxins. We demonstrate that heterooligomer formation modulates peroxoredoxin oligomeric state and enhances structural stability. In yeast, Tsa1-Tsa2 peroxiredoxin heterodecamers form in response to oxidative stress and incorporated Tsa2 stabilizes the decameric state. Beyond yeast, we show that human PRDX1 and PRDX2, as well as plant and parasitic peroxiredoxins, engage in functional heterooligomerization. These findings challenge the long-held paradigm of peroxiredoxin homooligomerization and reveal a novel mechanism for regulating redox homeostasis. Our study provides new insights into peroxiredoxin structural plasticity with broad implications for redox biology, stress responses, and cellular adaptation.

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Zimmermann, J., Lang, L., Malo Pueyo, J., Reidel, M., Wahni, K., Stobbe, D., Lux, C., Janvier, S., Vertommen, D., Lenhard, S., Hannemann, F., Castro, H., Tomas, A. M., Herrmann, J., Salvador, A., Muehlhaus, T., Riemer, J., Messens, J., Deponte, M., Morgan, B.. 2025-03-10. Heterooligomerization drives structural plasticity of eukaryotic peroxiredoxins. https://doi.org/10.1101/2025.03.03.641172

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