# Deciphering the role of amino acid transporters in mitochondrial myopathy

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $352,836

## Abstract

Project Summary
Mitochondria are centrally involved in the conversion of nutrients into energy, and thus, damage to this
organelle results in altered nutrient catabolism. The skeletal muscle system is prominently affected in the
setting of mitochondrial dysfunction, but little is known regarding the activity of metabolic pathways in diseased
muscular tissue. Our preliminary work has discovered that central carbon metabolism is altered in cultured
cells with pathogenic mitochondrial genome (mtDNA) mutations, and identified alterations in key members of
the solute transport carrier (SLC) family which regulate these perturbations. Importantly, similar alterations in
SLC family members, particularly the xc- transport system, occur in muscular tissues of subjects with
mitochondrial myopathy. Using mouse models of mitochondrial disease, we propose three specific aims to
characterize the role of xc- in altering metabolic fluxes in diseased skeletal muscle. In Aim 1, we will
characterize metabolic pathways in diseased animals using stable isotope labeling techniques. These results
will quantitate in vivo metabolism in mutant muscle tissue, providing a detailed mapping of the differences
between normal and diseased states. In Aim 2, we will investigate the role of xc- in regulating skeletal muscle
metabolism, making use of an available knockout allele. In Aim 3, we will test the hypothesis that altering xc-
activity modulates disease progression in diseased mice, by following muscular physiology and function in live
animals. Together, these aims will quantitate metabolic alterations in mitochondrial myopathies, and relate
them to in vivo muscle function and health. The results have the potential to identify new therapies targeting
carbon metabolism which may be beneficial for patients suffering from mitochondrial myopathies.

## Key facts

- **NIH application ID:** 10458552
- **Project number:** 5R01AR073217-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Prashant Mishra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $352,836
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458552

## Citation

> US National Institutes of Health, RePORTER application 10458552, Deciphering the role of amino acid transporters in mitochondrial myopathy (5R01AR073217-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10458552. Licensed CC0.

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