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bioRxiv · 10.1101/2021.01.30.428937

Surviving hypothermia by ferritin-mediated iron detoxification

Pekec, T.·Lewandowski, J.·Komur, A. A.·Sobanska, D.·Guo, Y.·Switonska-Kurkowska, K.·Frankowski, M.·Figiel, M.·Ciosk, R.
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Abstract

How animals rewire cellular programs to survive cold is a fascinating problem with potential biomedical implications, ranging from emergency medicine to space travel. Studying a hibernation-like response in the free-living nematode Caenorhabditis elegans, we 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 Fth1/ferritin. Moreover, we show that inducing expression of Fth1 also promotes cold survival of mammalian neurons, a cell type particularly sensitive to deterioration in hypothermia. Our findings in both animals and cells suggest that FTN-1/Fth1 facilitates cold survival by detoxifying ROS-generating iron species. We finally show that mimicking the effects of FTN-1/Fth1 with drugs protects neurons from cold-induced degeneration, opening a potential avenue to improved treatments of hypothermia.

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Pekec, T., Lewandowski, J., Komur, A. A., Sobanska, D., Guo, Y., Switonska-Kurkowska, K., Frankowski, M., Figiel, M., Ciosk, R.. 2021-02-01. Surviving hypothermia by ferritin-mediated iron detoxification. https://doi.org/10.1101/2021.01.30.428937

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