Heterooligomerisation is a conserved feature of eukaryotic typical 2-Cys peroxiredoxins

Peroxiredoxins are conserved thiol peroxidases for peroxide detoxification, redox signaling, and chaperone activity. Peroxiredoxin 1-type typical 2-Cys peroxiredoxins are present in both prokaryotes and eukaryotes, with multiple closely related isoforms often coexisting within the same subcellular compartment of a given species. While these peroxiredoxins have long been thought to form exclusively homooligomeric structures, emerging evidence challenges this view. We show that the formation of enzymatically active heterooligomers is a conserved feature of typical 2-Cys peroxiredoxins in eukaryotes and plays an important role in modulating peroxiredoxin oligomeric state. We used negative strain electron microscopy to visualize yeast Tsa1–Tsa2 peroxiredoxin heterodecamers and show that heterooligomer formation is inducible in response to oxidative stress. Our findings suggest that hetero oligomerization is a novel key regulatory mechanism for redox homeostasis and cellular adaptation, reshaping the structural and functional landscape of peroxiredoxins.