# The Biology of Peroxiredoxin 6

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $376,750

## Abstract

Project Summary/Abstract
Peroxiredoxin 6 (Prdx6) is a multi-functional enzyme that expresses glutathione peroxidase, phospholipase A2
(PLA2), and lysophosphatidylcholine acyltransferase (LPCAT) activities in separate catalytic sites. Prdx6 can
reduce phospholipid hydroperoxides and hydrolyze and re-acylate phospholipid fatty acyl bonds. Prdx6 is,
therefore, a complete enzyme for the repair of peroxidized cell membranes. Prdx6 has been implicated in
several pathophysiological conditions, including acute lung injury, inflammation, carcinogenesis, various
chronic central nervous system diseases, retinal disease, type 2 diabetes, muscle atrophy, and male infertility,
but basic questions about the biology of this unique enzyme remain unanswered. Our preliminary data strongly
suggest that Prdx6 suppresses ferroptosis, an iron-dependent form of regulated cell death driven by the
accumulation of phospholipid hydroperoxides. Emerging evidence implicates ferroptosis in several
degenerative diseases, carcinogenesis, stroke, traumatic brain injury, and ischemia/reperfusion injury, among
others. Hence, establishing the mechanisms and physiological relevance of ferroptosis regulation by Prdx6 is
crucial. My lab is interested in studying the role of the glutathione peroxidase, PLA2, and LPCAT activities of
Prdx6 on the regulation of ferroptosis induced by inhibition of cystine uptake, hypoxia/reoxygenation, and
oxygen toxicity. We will use mice and cells with single point mutations that inactivate each of the activities of
Prdx6 without affecting the others, along with state-of-the-art analytical tools to dissect the role of this enzyme
on the regulation of ferroptosis. In a second project, I propose to study the role of Prdx6 in the maintenance of
mitochondrial function. Our preliminary data show that Prdx6 deficiency alters transcriptional signatures of
mitochondrial metabolism and reduces mitochondrial respiration. We will study the effects of the catalytic
activities of Prdx6 on mitochondrial morphology, dynamics, and function using extracellular flux assays and
three-dimensional imaging techniques. The results of this proposal will contribute to our understanding of one
of the critical mediators of cellular redox balance. These results will also provide essential information for future
translational strategies for the prevention and treatment of diseases associated with dysregulated redox
homeostasis.

## Key facts

- **NIH application ID:** 10686366
- **Project number:** 5R35GM146951-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Jose P Vazquez Medina
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $376,750
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10686366

## Citation

> US National Institutes of Health, RePORTER application 10686366, The Biology of Peroxiredoxin 6 (5R35GM146951-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10686366. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*