Physiological relevance of peroxiredoxin hetero-oligomerisation

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Peroxiredoxins are among the top 1-10% of most abundant proteins in pro- and eukaryotes. They are central for (i) hydroperoxide detoxification and can also act (ii) as peroxide sensors in signal transduction and (iii) as chaperones during heat and/or oxidative stress. These three different physiological functions are coupled to a highly flexible quaternary structure that ranges from homo-dimers and -decamers to 1.0 MDa oligomers. Surprisingly, most eukaryotes have two or even three apparently redundant cytosolic peroxiredoxin isoforms. Although considered almost exclusively as independent entities, intriguingly we recently observed that the peroxiredoxins Tsa1 and Tsa2 from baker’s yeast readily form hetero-oligomers. We thus propose that peroxiredoxin redundancy is not a coincidence but rather that peroxiredoxin hetero-oligomerization is a mechanism that serves to greatly expand the functional plasticity of this protein family. Even though PubMed searches reveal more than 5000 publications on peroxiredoxins, there are, to the best of our knowledge, only two studies that have addressed the physiological formation of peroxiredoxin hetero-oligomers in yeast and in human cell lines. The physiological relevance of peroxiredoxin hetero-oligomerization is unknown to date. In the present project, we want to analyze whether peroxiredoxins can be really regarded as isolated entities or whether peroxiredoxin hetero-oligomers act as catalytic and modulatory integration hubs that link the molecular plasticity and functional versatility of peroxiredoxins.