# Role of peroxisome-mitochondrion communication in tissue aging

> **NIH NIH R01** · IOWA STATE UNIVERSITY · 2024 · $306,001

## Abstract

Project Summary/Abstract
 Inter-organelle communication plays an essential role in maintaining cellular homeostasis
and animal aging. Mitochondria, as a highly dynamic organelle and the metabolic hub of the cell,
frequently interact with other cellular organelles to coordinate metabolic processes and maintain
cellular homeostasis. Although it is well known that mitochondrial dynamics are often altered
during animal aging, it remains largely unanswered whether and how inter-organelle
communication plays a crucial role in age-dependent alternations of mitochondrial dynamics. Like
mitochondria, peroxisomes play an important role in redox and lipid metabolism (e.g., ether
phospholipid biosynthesis). However, peroxisome aging research is an understudied area. In this
proposal, we will combine CRISPR genome editing, organelle proteomics, metabolomics, and
cutting-edge imaging tools to investigate the important role of peroxisome-mitochondrion
communication in animal aging. The proposal is based on our previous exciting findings showing
that activation of peroxisomal receptor protein Pex5 not only rescued age-dependent decline of
peroxisomal import, but also preserved mitochondrial structure and function. We further show that
peroxisomal ether phospholipid biosynthesis is involved in the regulation of mitochondrial
dynamics. Furthermore, we uncovered a novel positive feedback loop that regulates the ether
phospholipid synthesis pathway under oxidative stress.
 In this proposal, we will address two outstanding questions: 1) Why and how does
peroxisomal import decline with age? 2) How does peroxisomal dysfunction contribute to cellular
aging? Could inter-organelle communication be a core mechanism? The proposed work will
provide novel insights into the significant role of peroxisome-mitochondrion communication in
animal health aging and longevity. Three specific aims are proposed: Specific Aim 1. Determine
how peroxisomal import function declines with age. Specific Aim 2. Determine the role of
peroxisome-derived ether phospholipids in age-related alterations of mitochondrial dynamics.
Specific Aim 3. Determine the role of ATF4 in transcriptional regulation of Gnpat and peroxisomal
ether phospholipid biosynthesis during aging.

## Key facts

- **NIH application ID:** 10892927
- **Project number:** 5R01AG075156-02
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** Hua Bai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $306,001
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892927

## Citation

> US National Institutes of Health, RePORTER application 10892927, Role of peroxisome-mitochondrion communication in tissue aging (5R01AG075156-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10892927. Licensed CC0.

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