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The genetically encoded biosensor FEOX is a molecular gauge for cellular iron environment dynamics at single cell
1Department of Pathology, University of California San Francisco, San Francisco, CA, USA. Carolyn.Sangokoya@ucsf.edu.
Scientific Reports
|October 21, 2025
Summary
Researchers developed FEOX, a novel biosensor to measure bioavailable iron within cells. This tool tracks cellular iron dynamics during stem cell differentiation, offering new insights into iron homeostasis.
Area of Science:
- Cellular biology
- Biochemistry
- Genetics
Background:
- Cellular iron levels are critical for biological processes and are sensed through conserved mechanisms.
- Iron regulatory proteins (IRPs) are key regulators of iron homeostasis, but tools to directly quantify intracellular iron are limited.
- Understanding dynamic changes in cellular iron is essential for studying development and differentiation.
Purpose of the Study:
- To develop a genetically-encoded biosensor for quantifying bioavailable intracellular iron at single-cell resolution.
- To investigate the dynamics of cellular iron during stem cell differentiation.
- To provide an orthogonal tool to assess iron status independent of IRP activity.
Main Methods:
- Development of FEOX, a ratiometric fluorescent biosensor utilizing a hemerythrin-like domain.
- Application of FEOX for real-time, single-cell measurements of intracellular iron during stem cell differentiation.
- Comparison of FEOX dynamics with an iron regulatory protein (IRP) activity sensor.
Main Results:
- FEOX successfully measured dynamic changes in bioavailable cellular iron.
- Decreased ratiometric fluorescence from FEOX correlated with iron-limiting conditions.
- FEOX and IRP sensor data indicated increased iron demand during stem cell differentiation.
- The biosensor provides a method to quantify cellular iron independent of IRP function.
Conclusions:
- FEOX is a valuable tool for assessing intracellular iron dynamics at single-cell resolution.
- This biosensor offers new avenues for studying iron homeostasis during development and differentiation.
- Genetically-encoded biosensors like FEOX enhance our understanding of mammalian iron metabolism.
