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Cellular and molecular mechanisms of cell damage and cell death in ischemia–reperfusion injury in organ transplantation

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A Correction to this article was published on 01 July 2024

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Abstract

Ischemia–reperfusion injury (IRI) is a critical pathological condition in which cell death plays a major contributory role, and negatively impacts post-transplant outcomes. At the cellular level, hypoxia due to ischemia disturbs cellular metabolism and decreases cellular bioenergetics through dysfunction of mitochondrial electron transport chain, causing a switch from cellular respiration to anaerobic metabolism, and subsequent cascades of events that lead to increased intracellular concentrations of Na+, H+ and Ca2+ and consequently cellular edema. Restoration of blood supply after ischemia provides oxygen to the ischemic tissue in excess of its requirement, resulting in over-production of reactive oxygen species (ROS), which overwhelms the cells’ antioxidant defence system, and thereby causing oxidative damage in addition to activating pro-inflammatory pathways to cause cell death. Moderate ischemia and reperfusion may result in cell dysfunction, which may not lead to cell death due to activation of recovery systems to control ROS production and to ensure cell survival. However, prolonged and severe ischemia and reperfusion induce cell death by apoptosis, mitoptosis, necrosis, necroptosis, autophagy, mitophagy, mitochondrial permeability transition (MPT)-driven necrosis, ferroptosis, pyroptosis, cuproptosis and parthanoptosis. This review discusses cellular and molecular mechanisms of these various forms of cell death in the context of organ transplantation, and their inhibition, which holds clinical promise in the quest to prevent IRI and improve allograft quality and function for a long-term success of organ transplantation.

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  1. Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana

    George J. Dugbartey

  2. Department of Physiology & Pharmacology, Accra College of Medicine, East Legon, Accra, Ghana

    George J. Dugbartey

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Dugbartey, G.J. Cellular and molecular mechanisms of cell damage and cell death in ischemia–reperfusion injury in organ transplantation. Mol Biol Rep 51, 473 (2024). https://doi.org/10.1007/s11033-024-09261-7

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