In vivo visualization of bioactive iron and oxygen using LiON, the labile iron and oxygen notifier

Iron and oxygen are essential for numerous biological processes, yet monitoring their bioactive intracellular dynamics in vivo remains challenging due to the limitations of current detection methods. Here, we introduce the labile iron and oxygen notifier (LiON), a genetically encoded, ratiometric fluorescent reporter enabling single-cell-resolution monitoring of intracellular iron and oxygen levels in vivo. In cultured cells, LiON responds dynamically to physiologically relevant changes in iron and oxygen levels. Using LiON-knockin mice, we revealed heterogeneous distribution of iron and oxygen across tissues, cell types, and even among individual cells of the same type. Thus, LiON offers a platform for studying iron and oxygen metabolism in living organisms, providing insights into the cellular diversity of iron and oxygen utilization and their roles in physiology and disease.