Dr. Jarosław Lewandowski, M. Eng. Alicja A. Komur, dr. Daria Sobańska and prof. Rafał Ciosk from the Integrative Biology Team of IBCH PAS, in collaboration with dr. Maciej Figiel and M. Eng. Karolina Świtońska-Kurkowska from Department of Molecular Neurobiology PAS, published the article „Ferritin-mediated iron detoxification promotes hypothermia survival in Caenorhabditis elegans and murine neurons” in Nature Communications [volume 13, article number: 4883 (2022), https://doi.org/10.1038/s41467-022-32500-z]. The research was initiated as part of the doctoral dissertation of dr. Tina Pekec from University of Basel, Faculty of Natural Sciences, Switzerland. Other authors who contributed to the research were: dr. Yanwu Guo and dr. Jędrzej M. Małecki from University of Oslo, Department of Biosciences, Norway; Abhishek Anil Dubey and prof. Wojciech Pokrzywa from Laboratory of Protein Metabolism, International Institute of Molecular and Cell Biology as well as prof. Marcin Frankowski from Adam Mickiewicz University in Poznań, Faculty of Chemistry.
How animals rewire cellular programs to survive cold is a fascinating problem with potential biomedical implications, including emergency medicine. Studying a hibernation-like process in the free-living nematode Caenorhabditis elegans, the authors uncovered a regulatory axis that enhances the natural resistance of nematodes to severe cold. This axis involves conserved transcription factors, DAF-16/FoxO and PQM-1, which jointly promote cold survival by upregulating FTN-1, a protein related to mammalian ferritin heavy chain (FTH1). Moreover, a research group proved that inducing expression of ferritin also promotes cold survival of mammalian neurons, a cell type particularly sensitive to deterioration in hypothermia. Scientists observations in both animals and cells suggest that FTN-1/FTH1 by binding free divalent iron ions facilitates cold survival as an aftermath of detoxifying ROS-generating iron species through the Fenton reaction. The article shows that mimicking the effects of FTN-1/FTH1 with antioxidant drugs, eg. deferoxamine – an iron chelator, protects neurons from cold-induced degeneration. Collected findings open a potential avenue to enhanced treatment and broader implementation of therapeutic hypothermia.