当前位置: X-MOL 学术ACS Sens. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
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
down
wechat
bug