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bioRxiv · 10.1101/2022.05.20.491061

Ratiometric NAD+ sensors reveal subcellular NAD+ modulators

Chen, L.·Chen, M.·Luo, M.·Li, Y.·Liao, B.·Hu, M.·Yu, Q.
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Abstract

Mapping NAD+ dynamics in live cells and human are essential for translating NAD+ interventions into effective therapies. Yet genetically encoded NAD+ sensors with better specificity and pH-resistance are still needed for cost-effective monitoring of subcellular and clinical NAD+. We introduce multicolor, resonance energy transfer-based NAD+ sensors that cover nano- to milli-molar 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+ supplements and modulators. Then, the sensors enabled high-throughput screenings for mitochondrial and nucleic NAD+ modulators and identified -GPC, a cognition-related metabolite, induces NAD+ redistribution from mitochondria to nucleus relative to the total adenine nucleotides, which was confirmed by NAD+ FRET microscopy.

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Chen, L., Chen, M., Luo, M., Li, Y., Liao, B., Hu, M., Yu, Q.. 2022-05-20. Ratiometric NAD+ sensors reveal subcellular NAD+ modulators. https://doi.org/10.1101/2022.05.20.491061

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