Restoring Mitochondrial Function While Avoiding Redox Stress: The Key to Preventing Ischemia/Reperfusion Injury in Machine Perfused Liver Grafts?

Autor: Hofmann J; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Otarashvili G; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Meszaros A; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Ebner S; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Weissenbacher A; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Cardini B; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Oberhuber R; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Resch T; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Öfner D; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Schneeberger S; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Troppmair J; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria., Hautz T; Department of Visceral, Transplant and Thoracic Surgery (VTT), Daniel Swarovski Research Laboratory (DSL), Medical University of Innsbruck (MUI), Innrain 66, A-6020 Innsbruck, Austria.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 Apr 29; Vol. 21 (9). Date of Electronic Publication: 2020 Apr 29.
DOI: 10.3390/ijms21093132
Abstrakt: Mitochondria sense changes resulting from the ischemia and subsequent reperfusion of an organ and mitochondrial reactive oxygen species (ROS) production initiates a series of events, which over time result in the development of full-fledged ischemia-reperfusion injury (IRI), severely affecting graft function and survival after transplantation. ROS activate the innate immune system, regulate cell death, impair mitochondrial and cellular performance and hence organ function. Arresting the development of IRI before the onset of ROS production is currently not feasible and clinicians are faced with limiting the consequences. Ex vivo machine perfusion has opened the possibility to ameliorate or antagonize the development of IRI and may be particularly beneficial for extended criteria donor organs. The molecular events occurring during machine perfusion remain incompletely understood. Accumulation of succinate and depletion of adenosine triphosphate (ATP) have been considered key mechanisms in the initiation; however, a plethora of molecular events contribute to the final tissue damage. Here we discuss how understanding mitochondrial dysfunction linked to IRI may help to develop novel strategies for the prevention of ROS-initiated damage in the evolving era of machine perfusion.
Databáze: MEDLINE
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