Hetero-oligomerization drives structural plasticity of eukaryotic peroxiredoxins

Peroxiredoxins are thiol peroxidases, which detoxify peroxides, relay redox signals and act as chaperones. In eukaryotes, multiple peroxiredoxin-1 (Prx1)/AhpC-type isoforms frequently co-exist in the same subcellular compartment, yet have been assumed to assemble only as homo-oligomeric complexes. Here we show that hetero-oligomerization is a conserved and functionally relevant property of Prx1/AhpC-type peroxiredoxins. Using biochemical reconstitution, native mass photometry, electron microscopy and live-cell assays, we demonstrate formation of heterodimers and heterodecamers, with diverse subunit stoichiometries, in peroxiredoxin pairs from different eukaryotic kingdoms. In Saccharomyces cerevisiae, oxidative challenge induces Tsa1-Tsa2 heterodecamerization with substoichiometric Tsa2 incorporation sufficing to stabilize the decameric state. Functional hetero-oligomers are also observed forming among human, plant and Leishmania peroxiredoxins. Our findings provide new insights into peroxiredoxin structural plasticity with broad implications for redox biology, stress responses and cellular adaptation, and also challenge the long-held paradigm of peroxiredoxin homo-oligomerization.