Super-Resolution Imaging to Reveal Mitochondrial Nucleoprotein Dynamics with Reactive Oxygen Species Regulation.

Understanding the biomolecular interactions in a specific organelle has been a long-standing challenge because it requires super-resolution imaging to resolve the spatial locations and dynamic interactions of multiple biomacromolecules. Two key difficulties, however, are that molecular probes suitable for super-resolution nanoscopy are rather rare, and more adversely the use of multiple probes complicates their cellular uptakes, biodistributions, and spectral distinctions. Here, we report a quinolinium derivative probe that is selectively enriched in mitochondria, and switches on in three different fluorescence modes in response to hydrogen peroxide (H2O2), protein, and nucleic acid, enabling the visualization of mitochondrial nucleoprotein dynamics. Stimulated emission depletion (STED) nanoscopy reveals that the proteins localize at mitochondrial cristae and largely fuse with nucleic acids to form nucleoproteins, whereas increasing H2O2 level leads to disassociation of nucleic acid-protein complexes.