PXD060978

PXD060978 is an original dataset announced via ProteomeXchange.

Title	The interactome of the Bakers' yeast peroxiredoxin Tsa1 implicates it in the redox regulation of intermediary metabolism, glycolysis and zinc homeostasis
Description	Zinc (Zn) is an essential nutrient supporting a range of critical processes. In the yeast Saccharomyces cerevisiae, Zn deficiency induces a transcriptional response mediated by the Zap1 activator, which controls a regulon of ~80 genes. A subset of these support zinc homeostasis by promoting zinc uptake and its distribution between compartments. The remainder are generally induced by severe zinc deficiency and mediate an "adaptive response" to enhance fitness of zinc deficient (ZnD) cells. The peroxiredoxin (PR) Tsa1 is a Zap1-regulated adaptive factor that is essential for the growth of ZnD cells. Tsa1 can function as an antioxidant peroxidase, protein chaperone, or redox sensor; the latter activity redox-regulates associated proteins such as Yap1 via a relay mechanism. We previously reported that glycolytic activity is decreased in ZnD cells, and that under these conditions Tsa1 downregulates glycolytic pyruvate kinase (Pyk1) to conserve phosphoenolpyruvate for aromatic amino acid synthesis. However, this Tsa1-mediated inhibition of Pyk1 makes a relatively minor contribution to fitness in low zinc, suggesting that Tsa1 regulates other processes important to adaptation. Consistent with this model, we found that the redox sensor function of Tsa1 was essential for growth of ZnD cells. Using an MBP-tagged version of Tsa1, we identified a novel redox-sensitive non-covalent interaction with Pyk1, and leveraged this system to identify multiple novel interacting partners. This interactome implicates Tsa1 in the regulation of critical processes, including many zinc-dependent metabolic pathways. Interestingly, Zap1 was a preferred Tsa1 target. Tsa1 strongly promoted the oxidation of Zap1 activation domain 2, and was essential for full Zap1 activity in severely ZnD cells. Our findings reveal a novel posttranslational response to zinc deficiency that is overlain on and interconnected with the Zap1-mediated transcriptional response.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_16:13:09.849.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD060978
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Greg Sabat
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: NEWT:4932;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-19 12:47:53	ID requested
⏵ 1	2026-09-06 16:13:10	announced

10.1093/mtomcs/mfaf028;

MacDiarmid CW, Wang Y, Taggart J, Vashisht A, Qing X, Wohlschlegel JA, Eide DJ, The interactome of the Bakers' yeast peroxiredoxin Tsa1 implicates it in redox regulation of intermediary metabolism, glycolysis, and zinc homeostasis. Metallomics, 17(8):(2025) [pubmed]

10.6019/PXD060978;

submitter keyword: Tsa1, Zap1, Saccharomyces cerevisiae, peroxiredoxin, label free IP proteomics,Zinc, redox regulation

David J. Eide
contact affiliation	Nutritional Sciences, College of Agricultural and Life Sciences, University of Wisconsin-Madison
contact email	eide@nutrisci.wisc.edu
lab head
Greg Sabat
contact affiliation	University of Wisconsin
contact email	gsabat@wisc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060978
     1. Label: PRIDE project
     2. Name: The interactome of the Bakers' yeast peroxiredoxin Tsa1 implicates it in the redox regulation of intermediary metabolism, glycolysis and zinc homeostasis