# The Role of the Mitochondrion in the Metabolic Stress Response to Burn Trauma

> **NIH NIH R35** · ARKANSAS CHILDREN'S HOSPITAL RES INST · 2023 · $10,010

## Abstract

PROJECT SUMMARY
The main objective of this Maximizing Investigators' Research Award (MIRA) is to provide new
mechanistic insight regarding the metabolic stress response to burn trauma. Specifically, the overarching goal
of this research program is to elucidate the role of the mitochondrion in burn-induced hypermetabolism and
metabolic dysfunction. Burns are a leading cause of non-fatal trauma in the United States. Today, even the
most severe burns are survivable. However, burn survivors endure a protracted recovery, where restoration of
function and quality of life are not readily achieved. Accordingly, there is a pressing need for new strategies
that reduce morbidity and hasten the recovery of burn survivors.
Recent data have implicated mitochondria as mediators of the metabolic stress response to burn trauma.
Indeed, altered bioenergetics are thought underlay the hypermetabolic response to burns, and may contribute
to burn-induced insulin resistance, altered lipid metabolism and muscle wasting. Further, mitochondrial stress
appears to impact cellular homeostasis post burn through the formation of oxygen radicals, and may contribute
to the systemic inflammatory response to burns by releasing fragments of mitochondrial DNA (mtDNA) into the
circulation.
This MIRA will support the development of innovative rodent models of isotopically labeled adipose tissue and
skeletal muscle. These models will be leveraged to trace the turnover, redistribution and oxidation of specific
substrates in response to burn injury. By combining these novel models with deuterium oxide dosing in vivo,
we will generate important data regarding synthesis rates of key mitochondrial proteins in multiple tissues in
response to burn trauma. By dovetailing measurements of substrate flux and mitochondrial carrier protein
turnover with direct measures of mitochondrial respiratory function, proton leak, membrane potential and
superoxide formation, we will elucidate the mechanistic basis of altered bioenergetics and metabolism in
response to burn injury. In addition, the utility of ambient temperature, protonophores and mitochondrial
targeted antioxidants as strategies to restore bioenergetics and metabolic function post burn will also rigorously
tested. Furthermore, blood and tissue samples collected from burn patients will be used to validate preclinical
data and to probe the role of mtDNA in the systemic inflammatory response to burn injury.
By bettering our mechanistic understanding of the metabolic stress response to burns this research program
will contribute new knowledge that may be leveraged to lessen the suffering and promote the recovery of burn
survivors. Moreover, since hypermetabolism is present in other forms critical illness, the new information
generated by this research program may have broader scientific and clinical impact.

## Key facts

- **NIH application ID:** 10810410
- **Project number:** 3R35GM142744-02S1
- **Recipient organization:** ARKANSAS CHILDREN'S HOSPITAL RES INST
- **Principal Investigator:** Craig Porter
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $10,010
- **Award type:** 3
- **Project period:** 2021-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810410

## Citation

> US National Institutes of Health, RePORTER application 10810410, The Role of the Mitochondrion in the Metabolic Stress Response to Burn Trauma (3R35GM142744-02S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10810410. Licensed CC0.

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