Feng Xueyan, Yi Deyu, Li Lele, Li Mengyuan
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China.
School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China.
Angew Chem Int Ed Engl. 2025 Mar 17;64(12):e202422651. doi: 10.1002/anie.202422651. Epub 2025 Jan 9.
Adenosine triphosphate (ATP), the primary energy currency in cells, is dynamically regulated across different subcellular compartments. The ATP interplay between mitochondria and endoplasmic reticulum (ER) underscores their coordinated roles in various biochemical processes, highlighting the necessity for precise profiling of subcellular ATP dynamics. Here we present an exogenously and endogenously dual-regulated DNA nanodevice for spatiotemporally selective, subcellular-compartment specific signal amplification in ATP sensing. The system allows for exogenous NIR light-controlled spatiotemporal localization and activation of the aptamer sensor in mitochondria or ER, while a specific endogenous enzyme in the organelles further drives signal amplification via the consumption of molecular beacon fuels, resulting in significantly enhanced sensitivity and spatial precision for the subcellular ATP profiling in the organelle of interest. Furthermore, we demonstrate the application of this system for robust monitoring of ATP fluctuations in mitochondria and ER following drug interventions. This advancement provides a powerful tool for improving our understanding of cellular energetics at the subcellular level and holds potential for the development of targeted therapeutics.
三磷酸腺苷（ATP）是细胞中的主要能量货币，在不同的亚细胞区室中受到动态调节。线粒体与内质网（ER）之间的ATP相互作用突显了它们在各种生化过程中的协调作用，这突出了对亚细胞ATP动态进行精确分析的必要性。在此，我们展示了一种外源性和内源性双重调控的DNA纳米器件，用于在ATP传感中进行时空选择性、亚细胞区室特异性信号放大。该系统允许通过外源性近红外光控制适体传感器在线粒体或内质网中的时空定位和激活，而细胞器中的特定内源性酶通过消耗分子信标燃料进一步驱动信号放大，从而显著提高了在感兴趣细胞器中进行亚细胞ATP分析的灵敏度和空间精度。此外，我们证明了该系统在药物干预后对线粒体和内质网中ATP波动进行稳健监测的应用。这一进展为增进我们对亚细胞水平细胞能量学的理解提供了一个强大工具，并具有开发靶向治疗药物的潜力。
