# Mitochondrial phospholipids, ROS, and disuse atrophy

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $228,750

## Abstract

Project Summary/Abstract
Maintenance of skeletal muscle is essential for health and plays a significant role in quality of life. Inactivity
promotes skeletal muscle atrophy that not only reduces mobility but also increases the propensity to develop
metabolic and cardiovascular diseases. Although skeletal muscle atrophy has broad clinical impact in the
increasingly sedentary and aging population, a pharmacologic therapy for muscle mass loss does not exist.
Reactive oxygen species (ROS) is one possible mechanism that induces muscle atrophy by accelerating
proteolysis and depressing protein synthesis. However, the molecular origin of disuse-induced ROS is
unknown. In this application, we will test our hypothesis that changes in mitochondrial phospholipid
composition is a mechanism by which disuse increases ROS and contributes to muscle atrophy. Preliminary
data show that mouse hindlimb unloading is sufficient to reduce the proportion of mitochondrial
phosphatidylethanolamine (PE). PE is a conically-shaped phospholipid that forms membrane curvatures and is
known to congregate at cristae where it facilitates enzymes of electron transport system (ETS). Skeletal
muscle-specific ablation of mitochondrial PE was sufficient to increase ROS and promote atrophy. In this
proposal we will: 1) determine whether mitochondrial ROS-scavenging is sufficient to prevent muscle atrophy
induced by mitochondrial PE depletion, and 2) determine whether increasing mitochondrial PE is sufficient to
protect mice from disuse-induced ROS production and atrophy. Findings from these studies have substantial
implications on the molecular mechanism responsible for muscle atrophy and how we develop treatment for
loss in skeletal muscle mass and contractile function.

## Key facts

- **NIH application ID:** 9999427
- **Project number:** 5R21AG063077-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Katsuhiko Funai
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,750
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999427

## Citation

> US National Institutes of Health, RePORTER application 9999427, Mitochondrial phospholipids, ROS, and disuse atrophy (5R21AG063077-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999427. Licensed CC0.

---

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