# Alcohol-Induced Mitochondrial Derangements Cause Alveolar Macrophage Dysfunction

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $70,359

## Abstract

PROJECT SUMMARY/ABSTRACT:
 Patients with alcohol use disorders (AUD) are 2-4 times more susceptible to developing respiratory
infections and acute respiratory distress syndrome, compared to non-alcoholic subjects. In the lung, alveolar
macrophages (AM) are the first line of cellular defense in the alveolar space, and they function to phagocytize
and clear invading pathogens. However, chronic alcohol ingestion increases mitochondria (MT)-derived
oxidative stress and MT dysfunction, which impairs AM phagocytosis and increases risk for infections. In the
proposed studies, the PI will examine the effects of alcohol-induced MT-derived oxidative stress on AM
phagocytic dysfunction and susceptibility to infections (Aim 1). The PI will then elucidate the molecular
mechanisms involved in alcohol-induced MT derangements, including fragmentation and dysfunction (Aim 2).
Finally, since transcription factor B1, mitochondrial (TFB1M) is a critical mediator of MT DNA and MT gene
transcription, the PI will determine the effect of alcohol on AM TFB1M expression and activity as modulated by
microRNAs (Aim 3). These hypotheses will be investigated by using a mouse model of chronic alcohol
consumption, an in vitro ethanol exposed mouse AM cell line, MH-S, and AM isolated from human subjects
with AUD. The objectives of the studies outlined in this proposal are to elucidate the molecular mechanisms
responsible for phagocytic dysfunction in alcoholic AM and identify novel and therapeutically targetable
molecules responsible for EtOH-induced MT dysfunction.
 If successful, the proposed studies will identify novel therapeutic targets for future translational studies
that could impact the management of patients with a history of AUD who are at risk for significant lung
disorders, even during continued alcohol use, or potentially patients with disorders characterized by similar MT
dysfunction.

## Key facts

- **NIH application ID:** 10091551
- **Project number:** 3R01AA026086-03S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Samantha M. Yeligar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,359
- **Award type:** 3
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10091551

## Citation

> US National Institutes of Health, RePORTER application 10091551, Alcohol-Induced Mitochondrial Derangements Cause Alveolar Macrophage Dysfunction (3R01AA026086-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10091551. Licensed CC0.

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