# Gatekeepers of Mitochondrial NAD+

> **NIH NIH DP2** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $79,250

## Abstract

Project summary
We are working on new in vivo methods to study the intermediary metabolite nicotinamide adenine dinucleotide
(NAD+). NAD+ is critical for cellular metabolism and health, and its decreased steady-state levels have been
linked to human pathologies such as neurodegeneration, cardiovascular disease, metabolic syndrome, and
cancer. NAD+ concentrations are highly compartmentalized by cell type, subcellular localization, and its protein-
bound or free fractions. A lack of methods that can monitor free NAD+ in cells with spatial and temporal
information has hindered our learning about the relevant pools, threshold concentrations, and fluctuations that
NAD+ may undergo leading to disease onset. This precludes our ability to identify treatments or approaches to
intervene before NAD+ levels are misregulated. In particular, there are no genetically-encoded methods for in
vivo mitochondrial NAD+ measurements. Free mitochondrial NAD+ is required for cellular respiration, and
diminished levels due to genetics, age, or infection can promote reductive metabolism. Thus, to address this gap
we will improve the brightness (Aim 1) of a variant of the current NAD+ sensor, which is able to monitor free
mitochondrial NAD+ in cells. We will also generate a series of constructs that will be used to test a new approach
for improving the dynamic range of fluorescent readout (Aim 2). Together, data from these the aims will identify
a feasible method to robustly obtain free mitochondrial NAD+ measurements in vivo.

## Key facts

- **NIH application ID:** 10301237
- **Project number:** 3DP2GM126897-02S1
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Xiaolu Ang Cambronne
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $79,250
- **Award type:** 3
- **Project period:** 2017-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301237

## Citation

> US National Institutes of Health, RePORTER application 10301237, Gatekeepers of Mitochondrial NAD+ (3DP2GM126897-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10301237. Licensed CC0.

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