# Studies on the impact of acetyl-cysteine on metabolism

> **NIH NIH R21** · DUKE UNIVERSITY · 2024 · $194,381

## Abstract

Cells integrate nutrient sensing and metabolism to coordinate proper cellular responses to a particular nutrient
source. One way this occurs is via post-translational modifications of proteins. Acetyl-lysine is among the most
studied modification and regulates dynamic processes ranging from chromatin and gene expression to
metabolism. Our preliminary data presented in this application expand upon the acetylation landscape and
describe a new protein modification called acetyl-cysteine. This modification is abundant across the proteome
and is enriched on proteins involved in metabolism. These early data reveal key gaps in our understanding of
the acetylation landscape: what is the tissue distribution of this new modification? Under which physiological
conditions does this modification change? Which proteins are modified? What is the cellular consequence of
cysteine hyperacetylation? Is this relevant for aging? There is a critical need to understand the full range of
protein modifications in order to better understand physiological nutrient sensing and how it is perturbed in the
setting of disease. Although it is widely accepted that lysine modifications can participate in intracellular nutrient
sensing and is dysregulated with aging, no data exists on acetyl-cysteine. Therefore, the single objective of this
exploratory grant application is to determine the site(s), consequences, and physiologic mediators of cysteine
acetylation. Aim 1 will investigate the prevalence of cysteine acetylation by tissue type and metabolic state. In a
complementary parallel approach, Aim 2 will characterize the effects of cysteine acetylation on protein activity.
This project is significant because it uncovers a previously overlooked protein modification. Furthermore, given
cysteine’s central role in redox homeostasis, it is poised to play a central role in metabolic homeostasis. We put
forth conceptual and technical innovations that will both follow directed hypotheses and allow unbiased discovery
of the most important aspects of this new protein modification. Successful completion of this project will reveal a
new aspect of intracellular signaling and metabolic homeostasis that could influence our understanding of redox
biology and metabolism during aging.

## Key facts

- **NIH application ID:** 10745731
- **Project number:** 5R21AG080334-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Matthew D Hirschey
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,381
- **Award type:** 5
- **Project period:** 2022-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10745731

## Citation

> US National Institutes of Health, RePORTER application 10745731, Studies on the impact of acetyl-cysteine on metabolism (5R21AG080334-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10745731. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*