Ferritin-mediated iron detoxification promotes hypothermia survival in Caenorhabditis elegans and murine neurons.
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Pekec et al. Nat Commun. 2022. 13.4883.pdf (2.59 MB)
Date
2022-08-19
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Nature Publishing Group
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 ferritin heavy chain (FTH1). 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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Citation
Pekec, T., Lewandowski, J., Komur, A.A. et al. Ferritin-mediated iron detoxification promotes hypothermia survival in Caenorhabditis elegans and murine neurons. Nat Commun 13, 4883 (2022). https://doi.org/10.1038/s41467-022-32500-z