Ayato Maeda was peering into the liver cells of a genetically engineered mouse when he saw it—a vivid mosaic of red and green glowing under the microscope, revealing a hidden world within living tissue. What looked like abstract art was, in fact, the first real-time map of labile iron and oxygen levels in individual cells, captured by a new fluorescent tool called LiON. Developed by Maeda and Professor Toshiro Moroishi at the Institute of Science Tokyo, LiON is transforming how scientists study two of life’s most vital elements.
Iron and oxygen fuel nearly every cellular process, from energy production to DNA repair. But when their balance goes awry, the consequences can be devastating—linked to cancer, neurodegeneration, liver disease, and aging. Until now, researchers could only measure total iron in dead tissue samples, missing the dynamic, biologically active forms that actually drive cellular function. Even advanced imaging techniques lacked the resolution to see differences between neighboring cells. With LiON, that’s changing.
The breakthrough lies in its design. LiON fuses a red fluorescent protein to a sensor domain from FBXL5—a natural protein whose stability depends on iron and oxygen availability. This red signal degrades when iron and oxygen are low. A second, stable green fluorescent protein serves as an internal reference. By measuring the ratio of red to green fluorescence, researchers can quantify labile ferrous iron and oxygen levels in real time, within living cells. The team published their findings in Cell Reports Methods on May 8, 2026, demonstrating LiON’s power in live mice.
What they found was striking: even within the same organ, iron and oxygen levels varied dramatically. In the liver, cells near portal veins showed higher iron accumulation and greater susceptibility to oxidative stress—insights that could reshape how we understand liver disease progression. This cellular heterogeneity, long suspected but never directly observed, is now visible thanks to single-cell resolution imaging in living organisms.
"Visualizing the distribution and heterogeneity of iron and oxygen provides new opportunities to advance our understanding of a wide range of diseases," said Moroishi, who sees LiON as more than just a research tool—it’s a platform. Because LiON can be genetically targeted to specific tissues, it opens doors for studying disease models with unprecedented precision. Imagine tracking iron dysregulation in early-stage tumors or monitoring oxidative stress in aging neurons, all in real time.
As the team refines LiON for broader use, its potential extends beyond the lab. One day, it could help identify new therapeutic targets or even guide personalized treatments for diseases rooted in metabolic imbalance. For now, it offers something equally vital: a clearer view of the invisible forces shaping our cellular lives.