# Protein Disulfide Bond Formation in the Reducing Environment of Cytoplasm

> **NIH NIH R15** · TEXAS TECH UNIVERSITY · 2022 · $444,573

## Abstract

ABSTRACT
Nearly every cellular process is controlled by thiol-based redox regulation. However, the mechanisms of
targeted cysteine oxidation in the reducing environments of cytosol, mitochondria, and nucleus remain unclear.
Hydrogen peroxide (H2O2) is known to induce oxidation of cysteines in proteins, but the precise physiological
mechanisms are not fully understood. This mild cellular oxidant is metabolized by six mammalian
peroxiredoxins (Prxs) as well as several glutathione peroxidases and catalases. Prxs are expressed in a cell
type- or tissue-specific manner, and their reduced forms are regenerated by thioredoxin, other thiol
oxidoreductases, or glutathione. Previous studies indicate that Prxs can directly interact with regulatory
proteins and participate in cellular signaling. Recently, the endoplasmic reticulum specific PrxIV (erPrxIV) was
shown to function in the pathway of disulfide bond formation by oxidizing cysteines in protein disulfide
isomerase, which further oxidized client proteins in the endoplasmic reticulum; together protein disulfide
isomerase and erPrxIV formed disulfides in cellular proteins. We identified a new form of the disulfide forming
PrxIV, cPrxIV, located in the cytosol. In preliminary studies, we found that cPrxIV is highly expressed in
elongating spermatids in testes and is conserved in placental mammals. We further characterized the
properties and expression patterns of this protein and generated a knockout mouse model to study the
physiological function of cPrxIV. By analogy to the endoplasmic reticulum form of this protein, we hypothesize
that cPrxIV catalyzes disulfide bond formation in the cytosol and this function is particularly important during
spermatogenesis. We propose to characterize cPrxIV and its role in disulfide bond formation and redox
homeostasis. Specifically, we intend to (i) determine if cPrxIV participates in disulfide bond formation in
vitro and in vivo; (ii) identify interacting client partners and a reductase for cPrxIV; and (iii) characterize the
redox metabolome of PrxIV KO mice.

## Key facts

- **NIH application ID:** 10439311
- **Project number:** 1R15GM146198-01
- **Recipient organization:** TEXAS TECH UNIVERSITY
- **Principal Investigator:** Sun Hee Yim
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $444,573
- **Award type:** 1
- **Project period:** 2022-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439311

## Citation

> US National Institutes of Health, RePORTER application 10439311, Protein Disulfide Bond Formation in the Reducing Environment of Cytoplasm (1R15GM146198-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10439311. Licensed CC0.

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