biostudies-literatureZou JHuman Frontier Science ProgramU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesU.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)United States Department of Defense | United States Air Force | AFMC | Air Force Office of Scientific ResearchNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteUnited States Department of Defense | United States Air Force | AFMC | Air Force Office of Scientific Research (AF Office of Scientific Research)U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and StrokeNINDS NIH HHSHuman Frontier Science Program (HFSP)U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)NIGMS NIH HHS1075-1083https://www.ebi.ac.uk/biostudies/studies/S-EPMC11004682biostudies-literatureUnknown42(7)Cellular sodium ion (Na⁺) homeostasis is integral to organism physiology. Our current understanding of Na⁺ homeostasis is largely limited to Na⁺ transport at the plasma membrane. Organelles may also contribute to Na⁺ homeostasis; however, the direction of Na⁺ flow across organelle membranes is unknown because organellar Na⁺ cannot be imaged. Here we report a pH-independent, organelle-targetable, ratiometric probe that reports lumenal Na⁺. It is a DNA nanodevice containing a Na⁺-sensitive fluorophore, a reference dye and an organelle-targeting domain. By measuring Na⁺ at single endosome resolution in mammalian cells and Caenorhabditis elegans, we discovered that lumenal Na⁺ levels iNature biotechnologyA DNA nanodevice for mapping sodium at single-organelle resolution.PMC11004682RGP0032/2022DP1 GM149751R01 GM1471971R01NS112139-01A1R21 HL161825FA9550-19-0003R01 NS1121391R01GM147197-01R21HL161825-01A1DP1GM149751R21 NS1144281R21NS114428-01Zou JRao RKrishnan YSmith JJMitra KVeetil ATOettinger DRamirez JRAnees PGupta PDKratsios PfalseA DNA nanodevice for mapping sodium at single-organelle resolution.Cellular sodium ion (Na⁺) homeostasis is integral to organism physiology. Our current understanding of Na⁺ homeostasis is largely limited to Na⁺ transport at the plasma membrane. Organelles may also contribute to Na⁺ homeostasis; however, the direction of Na⁺ flow across organelle membranes is unknown because organellar Na⁺ cannot be imaged. Here we report a pH-independent, organelle-targetable, ratiometric probe that reports lumenal Na⁺. It is a DNA nanodevice containing a Na⁺-sensitive fluorophore, a reference dye and an organelle-targeting domain. By measuring Na⁺ at single endosome resolution in mammalian cells and Caenorhabditis elegans, we discovered that lumenal Na⁺ levels i2024-01-01T00:00:00Z2024 Jul2025-04-04T15:02:11.93Z2025-04-04T15:02:11.93ZS-EPMC110046823773526510.1038/s41587-023-01950-1