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

Koen Hendriks*, Christian Joschko, Femke Hoogstra-Berends, Janette Heegsma, Klaas Nico Faber, R. H. Henning

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

4 Citaten (Scopus)
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Samenvatting

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.
Originele taal-2English
Artikelnummer1864
Aantal pagina's13
TijdschriftInternational Journal of Molecular Sciences
Volume21
Nummer van het tijdschrift5
DOI's
StatusPublished - 9-mrt-2020

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