# Mitochondrial biogenesis and transfer to promote muscle regeneration

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2024 · —

## Abstract

Fibroadipoprogenitors (FAPs) are muscle stem cells that play a central role in maintaining muscle
homeostasis. In systemic chronic illnesses as well as musculoskeletal injuries, FAPs mediate muscle
degeneration through differentiation into fibrotic and fatty tissue, leading to declining muscle function
which is associated with decreased quality of life and shortened lifespan. While the role of FAPs in
muscle degeneration has been increasingly characterized in the last decade, we have found that certain
stimuli including B-agonism and intermittent ischemia/reperfusion (pre-conditioning) can induce a beige
fat phenotype that promotes muscle regeneration in vitro as well as in vivo. We have shown that
beige-FAPs are capable of mitochondrial transfer which is thought to be a mechanism by which other
stem cells are able to rescue injured cells to promote regeneration. The objective of this project is to
define the role of mitochondrial function and transfer on the ability of FAPs to improve muscle
regeneration. To determine this, begin by defining the mechanisms by which B-agonism can stimulate
FAP mitochondrial transfer. We hypothesize that B-agonism will stimulate FAPs to a beige phenotype
that will promote mitochondrial biogenesis and the formation of tunneling nanotube machinery. We will
next determine the intrinsic properties of FAP mitochondria and impact of FAP-mitochondrial donation
on myogenic cell proliferation, differentiation, and myogenic commitment We hypothesize that beige-
FAPs contain both enhanced mitochondrial numbers, but also increased bioenergetics that promote
muscle stem cell proliferation and differentiation. Finally, we will evaluate how B-agonist treatment or
pre-conditioning can stimulate beige-FAPs mitochondrial transfer in vivo to improve outcomes in the
setting of ischemia-reperfusion injury. The proposed work is important as it will define the mechanism
by which beige-FAPs can promote muscle regeneration. An increased understanding of this
mechanism in vitro and in vivo may assist in the rational design of treatment strategies to improve
muscle degeneration.

## Key facts

- **NIH application ID:** 10584359
- **Project number:** 1I01BX006098-01
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Brian Feeley
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-10-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10584359

## Citation

> US National Institutes of Health, RePORTER application 10584359, Mitochondrial biogenesis and transfer to promote muscle regeneration (1I01BX006098-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10584359. Licensed CC0.

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