What the research is about
Iron is essential not only for red blood cells to carry oxygen, but also for cells to produce energy, replicate DNA, and support the immune system. Inside cells, however, some iron is readily available for use, while some is stored. It has long been extremely difficult to observe specifically the iron that cells can actually use inside a living body. Existing methods have had different limitations: some could not distinguish readily available iron from stored iron, while others could not track how iron was distributed among individual cells or how it changed over time.
To address this challenge, a research team led by Professor Toshiro Moroishi at Institute of Science Tokyo (Science Tokyo) developed LiON, a fluorescence-based technique that can simultaneously visualize the iron and oxygen available inside cells. The technology enabled the researchers to examine the iron and oxygen in individual cells in living mice.
Why this matters
When the researchers used LiON to observe tissues in mice, they found for the first time that even neighboring cells within the same liver can differ in the status of iron and oxygen available to them.
One particularly interesting finding was that cells near the liver’s entrance, on the portal vein side, tended to accumulate more iron than cells near its exit, on the central vein side. As a result, the cells on the portal vein side were also more vulnerable to oxidative stress caused by iron.
Scientists already knew that liver cells perform different functions depending on their location. However, this study is the first to reveal differences in iron at the single-cell level inside a living body. The findings challenge the common assumption that iron is used uniformly throughout the body and show that, even within the same organ, the iron environment differs from cell to cell.
What’s next
When iron is not used properly inside cells or accumulates in excessive amounts, it can damage them. Such disruptions in iron metabolism have been linked to cancer, neurodegenerative diseases, aging, and ferroptosis, a form of iron-dependent cell death.
Because LiON can track iron and oxygen inside living organisms in ways that were not previously possible, it is expected to help researchers better understand how diseases develop and support the development of new treatments and drugs. Revealing how individual cells use iron differently may also deepen our understanding of fundamental biological processes.
Comment from the researcher
Our bodies may appear to be made up of similar cells, but the amounts of available iron and oxygen conditions differ from cell to cell. LiON has enabled us to visualize these previously unseen differences between individual cells. We hope this technology will lead to a deeper understanding of how living systems work and how diseases develop.
(Toshiro Moroishi, Professor, Division of Cellular Dynamics, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo)
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