Hibernating mitochondria, the cool key to cellular protection and transplant optimization: Mitochondrial aspects of hibernators and non-hibernators in hypothermia

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    Abstract

    Organ transplantation is a lifesaving therapy for patients suffering from end-stage organ failure. However, during the process of transplantation, organs are exposed to prolonged ischemia and subsequent reperfusion injury (I/R), which is detrimental for organ quality. Key to this I/R damage is failure of mitochondrial function resulting in loss of ATP production and the production of reactive oxygen species (ROS). The cornerstone to reduce I/R damage remains the traditional philosophy to induce a forced hypometabolic state by cooling with ice. However, this showed to be suboptimal and new preservation techniques are needed. This thesis suggests hibernation.
    Hibernating species are able to alternate between states of low body temperature and low oxygen levels and fast rewarming to normal temperature and oxygen levels, without tissue damage. This thesis speculates that cellular protection during hibernation appears to affect cell metabolism through mitochondrial pathways, as mitochondria fulfill an important and well known role in survival via ATP production that fuels cellular processes, but conversely also as ROS producer and apoptosis regulator in I/R.
    Therefore, in this project we looked into mitochondrial function and malfunction in hibernator and non-hibernator derived cells at different temperatures. With special interest in ROS formation and DNA damage. Additionally, by using an in vitro model of porcine kidney transplantation, we tried to obtain more insights into mitochondrial behavior during organ transplantation, with special focus on temperature effects and induction of a hibernation-like state using the smelling gas H2S.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Henning, Rob, Supervisor
    • Leuvenink, Henri, Supervisor
    • van Goor, Harry, Supervisor
    Award date22-Mar-2021
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-641-9138-7
    DOIs
    Publication statusPublished - 2021

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