A 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 in each stage of the endolysosomal pathway exceed cytosolic levels and decrease as endosomes mature. Further, we find that lysosomal Na + levels in nematodes are modulated by the Na + /H + exchanger NHX-5 in response to salt stress. The ability to image subcellular Na + will unveil mechanisms of Na + homeostasis at an increased level of cellular detail.