Redox proteomics reveal a role for peroxiredoxinylation in stress protection
Gerhard Seisenbacher,
Zrinka Raguz Nakic,
Eva Borràs,
Eduard Sabidó,
Uwe Sauer,
Eulalia de Nadal,
Francesc Posas
Affiliations
Gerhard Seisenbacher
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain
Zrinka Raguz Nakic
Institute of Molecular Systems Biology, ETH Zürich, 8093 Zurich, Switzerland; ZHAW School of Life Sciences and Facility Management, Biosystems Technology, 8820 Wädenswil, Switzerland
Eva Borràs
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Centre of Genomic Regulation, Barcelona Institute of Science and Technology, 08003 Barcelona, Spain
Eduard Sabidó
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Centre of Genomic Regulation, Barcelona Institute of Science and Technology, 08003 Barcelona, Spain
Uwe Sauer
Institute of Molecular Systems Biology, ETH Zürich, 8093 Zurich, Switzerland
Eulalia de Nadal
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain; Corresponding author
Francesc Posas
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain; Corresponding author
Summary: The redox state of proteins is essential for their function and guarantees cell fitness. Peroxiredoxins protect cells against oxidative stress, maintain redox homeostasis, act as chaperones, and transmit hydrogen peroxide signals to redox regulators. Despite the profound structural and functional knowledge of peroxiredoxins action, information on how the different functions are concerted is still scarce. Using global proteomic analyses, we show here that the yeast peroxiredoxin Tsa1 interacts with many proteins of essential biological processes, including protein turnover and carbohydrate metabolism. Several of these interactions are of a covalent nature, and we show that failure of peroxiredoxinylation of Gnd1 affects its phosphogluconate dehydrogenase activity and impairs recovery upon stress. Thioredoxins directly remove TSA1-formed mixed disulfide intermediates, thus expanding the role of the thioredoxin-peroxiredoxin redox cycle pair to buffer the redox state of proteins.
