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Peroxiredoxins act as a post-translational modification in cytoplasmic protein quality control

ABSTRACT: The redox state of proteins is essential for their function and to guarantee cell fitness. In the endoplasmic reticulum, cells recognize and resolve undesirable cysteine oxidations by protein quality control machinery that involves protein disulfide isomerases. While disulfide bonds are uncommon in the reducing environment of the cytoplasm, they play a key role in redox signaling during oxidative stress and disease states. Using global proteomic analyses, here we show that the cytoplasmic peroxiredoxin Tsa1 covalently binds cysteine residues of hundreds of proteins, including metabolic enzymes, and acts as a protective chaperone to maintain protein function. Thioredoxins maintain the balance of this peroxiredoxin post-translational mark. Our study unveils a mechanism involving the peroxiredoxin-thioredoxin cycle in cytoplasmic protein quality control in eukaryotes

INSTRUMENT(S): LTQ Orbitrap Velos, LTQ Orbitrap Elite

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Eva Borràs

LAB HEAD: Eduard Sabido

PROVIDER: PXD034411 | Pride | 2025-01-27

REPOSITORIES: pride

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			Action	DRS
	170517_S_GSFP_01_02.raw	Raw
	170517_S_GSFP_01_02_Velos.msf	Msf
	170517_S_GSFP_02_02.raw	Raw
	170517_S_GSFP_02_02_Velos.msf	Msf
	171214_S_GSFP_01_01_45pto.msf	Msf

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Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A

Project description:Peroxiredoxins are modulators of aging in yeast and multicellular organisms. The mechanisms by which peroxiredoxins stimulate H2O2 resistance and slow down aging are, however, unclear. Here we show that the yeast peroxiredoxin Tsa1 boosts H2O2 resistance and prevents aging independent of cellular H2O2 levels, but in a manner dependent on H2O2 signaling. More specifically, we pin-point a role of Tsa1 in repressing nutrient signaling via protein kinase A (PKA) that governs both H2O2 resistance and longevity. Tsa1 controls PKA activity at the level of the catalytic subunits and Tpk1 is redox-modified by Tsa1 on a conserved cysteine residue (Cys243) in Tpk1 upon H2O2 addition boosting cellular H2O2 resistance. Tpk1 redox modification dephosphorylates a conserved threonine 241 in the activation loop reducing enzyme activity. We discuss these results in the context of an integrative view on aging where nutrient signaling pathways constitute hubs integrating information from multiple aging-related conduits.

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NTRC controls chloroplast redox homeostasis through the regulation of the redox balance of 2-Cys Prxs in Arabidopsis

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Project description:Protein S-thiolation is a post-translational thiol-modification that controls redox-sensing transcription factors and protects active site cysteine residues against irreversible oxidation. In B. subtilis, the MarR-type repressor OhrR was shown to sense organic hydroperoxides via formation of mixed disulfides with the redox buffer bacillithiol (Cys-GlcN-Malate) termed as S-bacillithiolation. We have studied changes in the transcriptome and redox proteome caused by the strong oxidant hypochloric acid (NaOCl), the active component of house-hold bleach. The OhrR-controlled peroxiredoxin OhrA was most strongly up-regulated by NaOCl stress and conferred specific protection against NaOCl. Inactivation of the OhrR repressor was caused by S-bacillithiolation of the redox-sensing Cys15 residue in response to NaOCl. Two cobalamin-independent methionine synthases MetE and YxjG were identified as S-bacillithiolated at their essential active site cysteines resulting in hypochlorite-induced methionine limitation. In summary, our studies show that S-bacillithiolation of OhrR and the methionine synthases is the major mechanism in protection against hypochlorite stress in B. subtilis. The B. subtilis 168 wild type strain was grown in minimal medium to OD500 of 0.4 and harvested before and 10 minutes after exposure to 50 µM NaOCl. Microarray hybridizations were performed in triplicate using RNA isolated from independent cultures.

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2022-02-16 | PXD021662 | Pride

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