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Open AccessArticle

Hibernator-Derived Cells Show Superior Protection and Survival in Hypothermia Compared to Non-Hibernator Cells

1
Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
2
Department of Surgery, University Medical Centre Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
3
Departments of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Int. J. Mol. Sci. 2020, 21(5), 1864; https://doi.org/10.3390/ijms21051864
Received: 30 January 2020 / Revised: 3 March 2020 / Accepted: 4 March 2020 / Published: 9 March 2020
(This article belongs to the Special Issue Targeting Mitochondria in Aging and Disease)
Mitochondrial failure is recognized to play an important role in a variety of diseases. We previously showed hibernating species to have cell-autonomous protective mechanisms to resist cellular stress and sustain mitochondrial function. Here, we set out to detail these mitochondrial features of hibernators. We compared two hibernator-derived cell lines (HaK and DDT1MF2) with two non-hibernating cell lines (HEK293 and NRK) during hypothermia (4 °C) and rewarming (37 °C). Although all cell lines showed a strong decrease in oxygen consumption upon cooling, hibernator cells maintained functional mitochondria during hypothermia, without mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential decline or decreased adenosine triphosphate (ATP) levels, which were all observed in both non-hibernator cell lines. In addition, hibernator cells survived hypothermia in the absence of extracellular energy sources, suggesting their use of an endogenous substrate to maintain ATP levels. Moreover, hibernator-derived cells did not accumulate reactive oxygen species (ROS) damage and showed normal cell viability even after 48 h of cold-exposure. In contrast, non-hibernator cells accumulated ROS and showed extensive cell death through ferroptosis. Understanding the mechanisms that hibernators use to sustain mitochondrial activity and counteract damage in hypothermic circumstances may help to define novel preservation techniques with relevance to a variety of fields, such as organ transplantation and cardiac arrest. View Full-Text
Keywords: hibernation; mitochondria; ischemia-reperfusion; hypothermia; reactive oxygen species; ferroptosis hibernation; mitochondria; ischemia-reperfusion; hypothermia; reactive oxygen species; ferroptosis
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MDPI and ACS Style

Hendriks, K.D.W.; Joschko, C.P.; Hoogstra-Berends, F.; Heegsma, J.; Faber, K.-N.; Henning, R.H. Hibernator-Derived Cells Show Superior Protection and Survival in Hypothermia Compared to Non-Hibernator Cells. Int. J. Mol. Sci. 2020, 21, 1864. https://doi.org/10.3390/ijms21051864

AMA Style

Hendriks KDW, Joschko CP, Hoogstra-Berends F, Heegsma J, Faber K-N, Henning RH. Hibernator-Derived Cells Show Superior Protection and Survival in Hypothermia Compared to Non-Hibernator Cells. International Journal of Molecular Sciences. 2020; 21(5):1864. https://doi.org/10.3390/ijms21051864

Chicago/Turabian Style

Hendriks, Koen D.W.; Joschko, Christian P.; Hoogstra-Berends, Femke; Heegsma, Janette; Faber, Klaas-Nico; Henning, Robert H. 2020. "Hibernator-Derived Cells Show Superior Protection and Survival in Hypothermia Compared to Non-Hibernator Cells" Int. J. Mol. Sci. 21, no. 5: 1864. https://doi.org/10.3390/ijms21051864

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