# Regulation of the retinal ganglion cell repair program by the mitochondrial protein Armcx1

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $391,479

## Abstract

Abstract
Retinal ganglion cells (RGCs), like most neurons, heavily rely on functions fulfilled by 
mitochondria. However, for unclear reasons the sensitivity of RGCs to mitochondrial dysfunction is 
higher than in others neuronal types. As a result, many blinding diseases that affect 
RGCs are accompanied by mitochondrial impairment. These diseases have very different etiologies 
but likely share a common pathophysiology that involves some aspect of mitochondrial 
biology. Nevertheless, we have little knowledge of the processes that regulate RGC 
mitochondria in vivo which has impeded the development of mitochondria-directed treatments to 
promote RGC repair. It is important therefore to understand how RGCs regulate mitochondrial 
function and dynamics in vivo as a step in defining regulatory nodes amenable to 
pharmaceutical intervention. RGC axons appear to be a prime target for these interventions as they 
are especially sensitive to degenerative stress. In these axons that extend to a considerable 
distance, it is crucial that mitochondria are appropriately distributed to serve the needs of the 
periphery. We recently highlighted the importance of this distribution for RGC repair. 
We demonstrated that increasing mitochondrial transport protects RGCs from degeneration and promote 
axonal regeneration (Cartoni et al. 2016). This study uncovered a key regulator of 
mitochondrial transport; a mammalian specific mitochondrial protein called Armadillo 
Repeat-Containing X Linked Protein 1 (Armcx1). We showed that it regulates axonal 
mitochondrial transport and that it is both necessary and sufficient for RGC survival 
and axonal regeneration after optic nerve injury. These findings suggest that Armcx1 
controls the mitochondrial distribution of a mitochondria based RGC repair program. Our long-term 
 research goal is to elucidate and manipulate the elements of this newly identified 
repair program to treat vision disorders. Despite the importance of Armcx1 in RGC repair after 
traumatic injury, little is known about the physiological functions of Armcx1 in healthy and 
diseased RGCs. Our overall objective is to evaluate how Armcx1 impacts RGC degeneration and repair 
as well as to decipher how this protein regulates mitochondrial dynamics and function. 
Based on our preliminary results, our central hypothesis is that Armcx1 regulates 
mitochondrial transport in demanding conditions such as diseases and/or axonal outgrowth. 
Specifically, we hypothesize that Armcx1 is a ubiquitous player in neuroprotection (Aim 1) and that 
it is a critical component of the normal RGC axonal outgrowth program (Aim 2). Finally, in an 
effort to understand the mechanism by which mitochondria promote RGC repair, we will analyze the 
axonal and somatic mitoproteome and identify direct and indirect Armcx1-binding partners in vivo 
(Aim 3).

## Key facts

- **NIH application ID:** 10762449
- **Project number:** 5R01EY030969-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Sidney M Gospe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $391,479
- **Award type:** 5
- **Project period:** 2022-03-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10762449

## Citation

> US National Institutes of Health, RePORTER application 10762449, Regulation of the retinal ganglion cell repair program by the mitochondrial protein Armcx1 (5R01EY030969-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10762449. Licensed CC0.

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