# Function of the oxidoreductase PYROXD1 in axon regeneration

> **NIH NIH F31** · YALE UNIVERSITY · 2022 · $46,752

## Abstract

Project Summary/Abstract
Through axon regeneration, neurons restore function after injury. This conserved, complex process requires
numerous cellular pathways including support of mitochondrial function and RNA processing. Mitochondria
function is implicated in numerous neurological disorders, and dysfunction of mitochondria contributes to
oxidative stress, a hallmark of aging. However, the role of the oxidative environment in axon regeneration has
not been well characterized. Oxidoreductases are a diverse class of enzymes that regulate the oxidative
environment of neurons. The oxidoreductase PYROXD1 is important for human health, and loss of PYROXD1
disrupts mitochondrial function and RNA-ligation by RtcB during the unfolded protein response. We found that
PYROXD1 is necessary for axon regeneration; however, the mechanism by which PYROXD1 promotes
regeneration is unknown. This proposal will elucidate the mechanism of PYROXD1 in axon regeneration in two
independent aims. In Aim 1, the role of PYROXD1 in mitochondria function and localization in axons during injury
will be determined. Mitochondria are critical for axon regeneration, and PYROXD1 is required for normal
mitochondria function. Aim 1 will establish the relationship between PYROXD1 and mitochondria during axon
regeneration, and will examine a suite of clinically-significant PYROXD1 mutations in this process. In Aim 2, the
role of PYROXD1-protection of the RNA-ligase RtcB will be clarified. RtcB inhibits axon regeneration via a novel
mechanism of non-canonical cytoplasmic splicing during the unfolded protein response. RtcB is dependent on
copper, and this dependence makes it sensitive to inactivation in oxidative environments. Aim 2 will determine
the sensitivity of RtcB to redox environment in vivo and define the relationship among PYROXD1, RtcB, and the
unfolded protein response gene xbp-1 in regeneration. Upon completion of this fellowship, the trainee will have
received extensive training in a supportive and collaborate environment. The project will further the trainee’s
technical skills, critical thinking abilities, and independence in preparation for an academic career in molecular
neuroscience. The results of this project will shed light on the importance of oxidative environment, mitochondria
function, and RNA processing for successful axon regeneration.

## Key facts

- **NIH application ID:** 10465346
- **Project number:** 1F31NS127495-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Carrie Ann Davison
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465346

## Citation

> US National Institutes of Health, RePORTER application 10465346, Function of the oxidoreductase PYROXD1 in axon regeneration (1F31NS127495-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465346. Licensed CC0.

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