Nat Biotechnol. 2023 Sep 21. doi: 10.1038/s41587-023-01950-1. Online ahead of print.

ABSTRACT

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.

PMID:37735265 | DOI:10.1038/s41587-023-01950-1