Ratiometric NAD+ Sensors Reveal Subcellular NAD+ Modulators,ACS Sensors

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Ratiometric NAD+ Sensors Reveal Subcellular NAD+ Modulators
ACS Sensors ( IF 8.2 ) Pub Date : 2023-03-17 , DOI: 10.1021/acssensors.2c02565
Liuqing Chen _{1,

2} , Meiting Chen ₁ , Mupeng Luo ₁ , Yong Li ₁ , Bagen Liao ₃ , Min Hu ₃ , Qiuliyang Yu _{1,

2}

Affiliation

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.

中文翻译：

比例 NAD+ 传感器揭示亚细胞 NAD+ 调制器

绘制活细胞和人体中的 NAD ^{+动态图对于将 NAD}⁺干预措施转化为有效疗法至关重要。然而，仍然需要具有更好特异性和 pH 耐受性的基因编码 NAD ⁺传感器，以经济有效地监测亚细胞区室和临床样本中的NAD ^{+ 。}在这里，我们介绍了多色、基于共振能量转移的 NAD ⁺传感器，涵盖纳摩尔到毫摩尔浓度范围，用于临床 NAD ⁺测量和亚细胞 NAD ⁺可视化。传感器捕获了 NMN 补充剂诱导的血液 NAD ⁺增加，并揭示了 NAD 的独特亚细胞效应⁺前体和调节剂。然后，传感器能够对线粒体和核 NAD ⁺调节剂进行高通量筛选，并鉴定出 α-GPC，这是一种认知相关代谢物，可诱导 NAD ⁺从线粒体到细胞核相对于总腺嘌呤核苷酸的重新分布，这一点进一步被 NAD ⁺证实FRET显微镜。

更新日期：2023-03-17

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