# Investigating the mechanisms of peroxisome homeostasis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2023 · $13,603

## Abstract

R35 Parent Grant – Project Summary: Investigating the mechanisms of peroxisome
homeostasis
The overarching goal of my lab is to understand how cells make and maintain peroxisomes, a
ubiquitous membrane-bound organelle that harbors specialized metabolic reactions.
Peroxisomes are both versatile and dynamic: cells use them to adapt to their environment, and
thus can rapidly remodel their peroxisomes by altering enzyme content, morphology, and
number through peroxisome-specific autophagy and de novo biogenesis. Approximately 35 Pex
proteins are known to contribute to peroxisome formation and maintenance, yet the
mechanisms by which they act are not resolved at a molecular level. Furthermore, we are likely
missing many important players, especially in human cells, and this lack of basic mechanistic
knowledge hinders our understanding of how peroxisome contribute to human health, both in
rare, genetic Peroxisome Biogenesis Disorders (PBDs), and during the aging process. Our
approach is to use techniques in protein biochemistry and yeast cell biology to dissect the
mechanism of the Pex proteins, particularly focusing on the AAA-ATPase Pex1/Pex6. We aim
to identify the full repertoire of Pex1/Pex6’s endogenous substrates and the features that are
important for substrate selection. Since mutations in Pex1/Pex6 cause the majority of PBDs, we
are further focused on using disease-causing alleles to understand Pex1/Pex6 function in the
human cells and the cellular consequences of peroxisome stress induced by these alleles.
Finally, we have identified novel regulators of peroxisome homeostasis in human cells, and are
now exploring how peroxisome function integrates with the implicated canonical signaling
pathways. We anticipate that this research will improve our understanding of how peroxisomes
contribute to human health and disease.

## Key facts

- **NIH application ID:** 10808484
- **Project number:** 3R35GM146784-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Brooke Meghan Gardner
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $13,603
- **Award type:** 3
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808484

## Citation

> US National Institutes of Health, RePORTER application 10808484, Investigating the mechanisms of peroxisome homeostasis (3R35GM146784-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10808484. Licensed CC0.

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