Subcellular Compartment‐Specific Amplified Imaging of Metal Ions via Ribosomal RNA‐Regulated DNAzyme Sensors

Abstract Although DNAzyme sensors have been widely developed for imaging metal ions, their application in specific subcellular compartments remains challenging due to low spatial controllability. Here we present a locally activatable, DNAzyme‐based sensing technology that enables subcellular compartment‐specific imaging of metal ions through ribosomal RNA (rRNA) regulated signal amplification. The system leverages a subcellularly encoded rRNA to locally activate DNAzyme‐based sensors, and further drives signal amplification via multiple turnover cleavage of molecular beacons, to significantly enhance sensitivity and spatial precision for metal‐ion imaging in specific organelles (e.g. mitochondria) or membraneless compartments (e.g. cytosol). Furthermore, we demonstrate that the system allows in situ monitoring of subcellular dynamics of mitochondrial Zn 2+ during ischemia and the drug intervention. This study expands the DNAzyme toolbox for investigating the role of subcellular metal‐ion dynamics in disease processes.