Unraveling Ferroptosis: Tracing Back Cell Death in Human Pathology
A team of Helmholtz Munich scientists has made a significant advancement in the understanding of ferroptosis, a complex form of cell death, by successfully detecting it retrospectively in human pathological conditions. This pioneering research, conducted in collaboration with pathologists at the Goethe University in Frankfurt and the Ludwig-Maximilians-University in Munich, sheds new light on the elusive nature of ferroptosis and its implications for disease. The results were now published in the journal Cell Death & Disease.
Ferroptosis, although recognized as a readily triggered phenomenon in laboratory settings, has faced challenges in gaining full acceptance within the biomedical community. One of the main obstacles has been the difficulty in detecting its presence in human pathological conditions. Unlike typical signaling pathways, ferroptosis is a rapid biochemical reaction in cells, making it challenging to retrospectively identify its byproducts.
FABP5 - A Key Biomarker for Ferroptosis
In a long-running study, the team of researchers around Dr. Joel Schick, Group Leader in the Research Unit “Signaling and Translation” at Helmholtz Munich, successfully identified a specific biomarker for ferroptosis in vivo. The key protein identified during this process is the fatty acid binding protein five (FABP5), which exhibited upregulation during the progression of ferroptosis. This finding was observed not only in laboratory cells but also in a unique patient cohort – individuals who experienced cerebral hypoxia following cardiac arrest, prior to passing. In effect, dying twice.
Prior to this study, a definitive marker had not been identified to detect ferroptosis’ contribution to disease. This highly representative human pathology cohort provided a unique opportunity to detect ferroptosis in humans. Additionally, as most pathological investigations are conducted on paraffin-embedded tissue, the identification of FABP5 as a reliable marker enables the retrospective detection of ferroptosis in tissues.
Disease Understanding and Therapeutic Implications
These findings mark a significant milestone in the study of ferroptosis and its implications for human diseases. The retrospective detection of this enigmatic form of cell death opens doors for further research and potential therapeutic interventions.
“Our discovery of a specific biomarker for ferroptosis in human pathological conditions represents a significant breakthrough in our understanding of this complex form of cell death,” states Hao Peng, the first author of the study.
“With this study we identified an important new tool to characterize the role of ferroptosis. This finding brings us closer to unraveling the mysteries of ferroptosis and its implications for human diseases”, adds Dr. Schick.
Original publication
Peng, H., Xin, S., Pfeiffer, S. et al. Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia. Cell Death Dis 15, 286 (2024). https://doi.org/10.1038/s41419-024-06681-y
About the scientist
Dr. Joel Schick, Group Leader in the Research Unit “Signaling and Translation” at Helmholtz Munich
Contact: joel.schick@helmholtz-munich.de
Funding information
This project was supported by the German Research Foundation (DFG, Project 501860452) to J. Schick, T. Arzberger, and S. Momma and DFG (511521600) to J. Schick, the EnABLE initiative by the state of Hessen to S. Momma, and Helmholtz Center Munich to J. Schick, Genetics and Cell Engineering Group.
Helmholtz Munich | ©Joel Schick