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- Title
Ferritin-mediated iron detoxification promotes hypothermia survival in Caenorhabditis elegans and murine neurons.
- Authors
Pekec, Tina; Lewandowski, Jarosław; Komur, Alicja A.; Sobańska, Daria; Guo, Yanwu; Świtońska-Kurkowska, Karolina; Małecki, Jędrzej M.; Dubey, Abhishek Anil; Pokrzywa, Wojciech; Frankowski, Marcin; Figiel, Maciej; Ciosk, Rafal
- 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. Strategies to improve cold resistance are of potential biomedical interest. Here the authors demonstrate that ferritin-mediated detoxification of iron, preventing the generation of reactive oxygen species, promotes cold survival in both Caenorhabditis elegans and cultured mammalian neurons.
- Subjects
CAENORHABDITIS elegans; IRON; HYPOTHERMIA; NEURONS; REACTIVE oxygen species; RETICULOCYTES
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-32500-z