LiON: A fluorescent molecule for tracking iron and oxygen levels in individual cells

A new fluorescent reporter capable of visualizing biologically active iron and oxygen inside living cells at single-cell resolution has been developed, as reported by researchers from Science Tokyo. Using this new tool, they revealed striking differences in the distribution of iron and oxygen across organs and even between neighboring cells of the same type. This innovation could serve as a platform for studying cancer, liver diseases, neurodegeneration, and aging.

Iron and oxygen are two of the most essential ingredients for life. Nearly every cell in the body depends on them to produce energy, regulate metabolism, and replicate DNA. Iron and oxygen are also deeply tied to diseases; disruptions in how cells handle these elements have been linked to cancer, liver problems, neurodegenerative disorders, and aging-related conditions. A solid understanding of how individual cells manage iron and oxygen could therefore open new doors in medicine and biotechnology.

However, most existing methods for detecting iron require fixed tissue samples, meaning researchers can only look at snapshots of dead tissue rather than intact living cells. Modern imaging technologies such as magnetic resonance imaging do offer a broader view in real time, but they cannot zoom in to the scale of single cells. Perhaps most critically, nearly all current tools measure total iron without distinguishing between the biologically active (labile ferrous iron) and inactive stored forms. Scientists have long suspected that even neighboring cells within the same tissue can have very different iron and oxygen environments, but there was simply no way to observe this directly.

To address this, a research team led by Professor Toshiro Moroishi from Division of Cellular Dynamics, Medical Research Laboratory, the Institute of Integrated Research, Institute of Science Tokyo (Science Tokyo), Japan, and doctoral student Ayato Maeda (at the time of the study; currently a project researcher at Science Tokyo), has developed an innovative fluorescent reporter that can simultaneously track labile iron and oxygen in living tissues with single-cell resolution. Their study, published online in the journal Cell Reports Methods on May 8, 2026, introduces this new tool called LiON, which stands for “labile iron and oxygen notifier.”

LiON works by leveraging a natural domain found in the iron- and oxygen-sensing protein FBXL5, whose stability inside cells depends on how much iron and oxygen are available. The researchers fused this sensing domain to a red fluorescent protein and then linked it to an inherently stable green fluorescent protein. Because the degradation of FBXL5 also destroys the red fluorescent compound, the ratio of red to green fluorescence provides a quantitative readout of labile ferrous iron and oxygen in the cell.

By genetically engineering mice to produce LiON, the team discovered striking variation in iron and oxygen levels not only between different organs, but also among individual cells of the same type within the same tissue. For example, they observed a clear spatial gradient in liver tissues, with cells near portal veins accumulating more iron and exhibiting greater vulnerability to oxidative stress. “Visualizing the distribution and heterogeneity of iron and oxygen provides new opportunities to advance our understanding of a wide range of diseases, including liver disorders, cancer, aging-related conditions, and neurodegenerative diseases,” remarks Moroishi.

The broader value of LiON lies in its versatility, since the reporter can be selectively activated in specific tissues using standard genetic tools. “We anticipate that LiON will be broadly applied to disease models and contribute to the development of novel therapeutic strategies,” concludes Moroishi.

With further development, LiON could become a foundational tool for studying how iron and oxygen regulation shapes cellular health across biology and medicine.

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About Institute of Science Tokyo (Science Tokyo)

Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, following the merger between Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the mission of “Advancing science and human wellbeing to create value for and with society.”