# The Role of Mitochondrial Dysfunction in Physical Recovery after Critical Illness

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

PROJECT SUMMARY
 Each year, over 100,000 Veterans survive an intensive care unit (ICU) stay for critical illness, but up to
half develop devastating and persistent impairments in physical function. Rehabilitation studies have
demonstrated limited efficacy to date, and little is known about the mechanistic underpinnings that link critical
illness and persistent physical function impairment. Improved understanding of underlying mechanisms is
urgently needed to improve long-term outcomes and allow for the development of effective interventions.
 During critical illness due, patients suffer from profound impairments in energy generation in skeletal
muscle due to disruptions in oxidative phosphorylation that leads globally reduced mitochondrial oxidative
capacity. Whether mitochondrial oxidative capacity normalizes in survivors, however, is unknown. Our
preliminary data indicates that ICU survivors suffer from impaired mitochondrial oxidative capacity as a form of
bioenergetic failure that limits physical recovery months after hospitalization.
 The hypothesis for this career development proposal is that reduced mitochondrial oxidative capacity in
survivors of critical illness is associated with worse physical function. To test this hypothesis, we will conduct
the “Altered energy Metabolism and PhysicaL Function in recoverY after the ICU” (AMPLiFY-ICU) prospective,
observational cohort study. We will enroll 62 Veterans who have survived critical illness and measure
mitochondrial oxidative capacity using skeletal muscle 31P-magnetic resonance spectroscopy (31P-MRS) and
peripheral blood mononuclear cell oxygen consumption via extracellular flux analysis at 3 months post-
discharge and determine their association with physical function at 6-month follow-up. Aim 1 will test the
hypothesis that reduced muscle-specific mitochondrial oxidative capacity, measured using 31P-MRS 3 months
post discharge is associated with worse physical function (measured by the primary outcome of six-minute
walk distance, 6MWD) at 6-month follow-up. Aim 2 will test the hypothesis that reduced systemic mitochondrial
oxidative capacity measured in peripheral blood mononuclear cells (PMBCs) at 3 months post-discharge is
associated with reduced physical function at 6-month follow-up. Aim 3 will explore whether reduced mobility in
the ICU is associated with reduced mitochondrial oxidative capacity (31P-MRS & PBMCs) at 3-month follow-up.
 The goal of the study outlined in this proposal is characterize the role of mitochondrial capacity on long-
term physical function after critical illness and its association with ICU mobility. This work will advance the field
by utilizing novel research approaches to characterize understudied mechanisms of physical recovery and
provide a foundation for physiologically targeted interventions. This proposal will also foster Dr. Mart’s scientific
career development by providing him the training, mentorship, and resources necessary to pursue a career
mer...

## Key facts

- **NIH application ID:** 10861202
- **Project number:** 1IK2RX004799-01A1
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Matthew Franklin Mart
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861202

## Citation

> US National Institutes of Health, RePORTER application 10861202, The Role of Mitochondrial Dysfunction in Physical Recovery after Critical Illness (1IK2RX004799-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10861202. Licensed CC0.

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