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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 ten identical subunits arranged in a donut-like ring. The new study challenges this view. 

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. 

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.