Ratiometric NAD+ Sensors Reveal Subcellular NAD+ Modulators

Mapping NAD+ dynamics in live cells and human is essential for translating NAD+ interventions into effective therapies. Yet, genetically encoded NAD+ sensors with better specificity and pH resistance are still needed for the cost-effective monitoring of NAD+ in both subcellular compartments and clin...

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Bibliographic Details
Published in:ACS sensors 2023-04, Vol.8 (4), p.1518-1528
Main Authors: Chen, Liuqing, Chen, Meiting, Luo, Mupeng, Li, Yong, Liao, Bagen, Hu, Min, Yu, Qiuliyang
Format: Article
Language:English
Subjects:
Cell Nucleus - metabolism
Cytosol - metabolism
Energy Transfer
Humans
Mitochondria - metabolism
NAD - metabolism
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Summary:Mapping NAD+ dynamics in live cells and human is essential for translating NAD+ interventions into effective therapies. Yet, genetically encoded NAD+ sensors with better specificity and pH resistance are still needed for the cost-effective monitoring of NAD+ in both subcellular compartments and clinical samples. Here, we introduce multicolor, resonance energy transfer-based NAD+ sensors covering nano- to millimolar concentration ranges for clinical NAD+ measurement and subcellular NAD+ visualization. The sensors captured the blood NAD+ increase induced by NMN supplementation and revealed the distinct subcellular effects of NAD+ precursors and modulators. The sensors then enabled high-throughput screenings for mitochondrial and nuclear NAD+ modulators and identified α-GPC, a cognition-related metabolite that induces NAD+ redistribution from mitochondria to the nucleus relative to the total adenine nucleotides, which was further confirmed by NAD+ FRET microscopy.
ISSN:2379-3694
2379-3694
DOI:10.1021/acssensors.2c02565