Not one ring but many: Antioxidant enzyme family can assemble in far more diverse ways than previously thought

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Peroxiredoxins are among the most abundant enzymes involved in managing oxidative stress. They control the levels of peroxides such as hydrogen peroxide, relay redox signals, and help protect other proteins during stress. For decades, scientists assumed that these enzymes assemble exclusively into complexes composed of 10 identical subunits arranged in a donut-like ring. A new study challenges this view.

Scientists from VIB, Vrije Universiteit Brussel, Saarland University, and RPTU University Kaiserslautern-Landau have discovered that this important family of antioxidant enzymes can assemble in far more diverse ways than previously thought. Their study is published in Nature Chemical Biology.

Using biochemical reconstitution, native mass photometry, electron microscopy, and live-cell experiments, the researchers demonstrated that peroxiredoxin variants can instead assemble into heterooligomers, mixed complexes containing different protein isoforms. This ability allows cells to create molecular heterogeneity without needing entirely new proteins.

"Peroxiredoxins are some of the most abundant redox enzymes in the cell and discovering that they mix and match subunits adds a whole new layer to how we think about redox regulation," says Bruce Morgan from Saarland University. "From an evolutionary perspective, it's a striking example of molecular Lego-like behavior in which cells generate complexity and functional diversity from just a handful of simple protein modules."

A conserved mechanism across species

The researchers observed this behavior across a wide range of organisms, including yeast, humans, plants, and protozoan parasites.

According to Marcel Deponte from RPTU University Kaiserslautern-Landau, mixing different protein variants allows cells to subtly tune the properties of these enzymes. "Different peroxiredoxin isoforms have slightly different biochemical behaviors," he explains. "When they assemble into mixed complexes, these properties effectively blend. This provides cells with a powerful way to fine-tune redox signaling and stress responses in a highly dynamic and context-dependent way."

Expanding the structural landscape

The discovery also highlights how protein assembly contributes to cellular adaptability. When different subunits combine, the number of possible structures increases dramatically.

"Hetero-oligomerization expands the structural possibilities enormously," says Joris Messens, group leader at the VIB-VUB Center for Structural Biology. "If only two types of protein subunits assemble into a ten-unit complex, varying both their ratio and position, cells can theoretically produce over a hundred distinct complexes. In other words, a small set of building blocks can generate a remarkably diverse range of structures."

The findings raise new questions about how cells organize redox signaling. If peroxiredoxins exist as heterogeneous mixtures rather than uniform complexes, scientists will need to better understand which assemblies dominate under physiological stress and how cells regulate their formation.

Deciphering this molecular "mix-and-match" system may provide new insights into diseases where redox balance is disrupted, including cancer, aging, and metabolic disorders.

Publication details

Jannik Zimmermann et al, Hetero-oligomerization drives structural plasticity of eukaryotic peroxiredoxins, Nature Chemical Biology (2026). DOI: 10.1038/s41589-026-02157-6. www.nature.com/articles/s41589-026-02157-6

Journal information: Nature Chemical Biology

Provided by VIB (the Flanders Institute for Biotechnology)