Organ transplantation is the only treatment for patients with severe and irreversible organ damage. Although the efficacy of transplantation has progressed immensely in recent years, one of the most damaging factors occurring during this surgical procedure, ischaemia reperfusion injury (IRI), is still a major contributor causing poor outcome. Ischaemia arises due to the lack of blood supply, leaving the tissue without oxygen and substrates, which are crucial for energy generation. Upon reperfusion with oxygenated blood, molecular processes within mitochondria lead to the generation of reactive oxygen species (ROS), which damage the organelles and lead to cell death and ultimately tissue fibrosis. During organ transplantation, the organs are cut off the blood supply when retrieved from a donor and stored at cold temperatures while transported to the recipient. During this time the organs become ischaemic and are then exposed to reperfusion injury within the recipient. Effective therapeutics to ameliorate this injury are not available, because of our lack of understanding of some of the basic underlying molecular processes during ischaemia, as well as the damaging pathways activated by factors released upon mitochondrial damage, such as succinate or mtDNA. In order to understand these processes better and be able to develop novel therapies, I utilised a range of models for IRI in heart, liver and kidney organ transplantation. These ranged from basic cell models to advanced in vivo procedures that closely replicated conventional transplantation. Finally, I compared these situations with data collected from human organs and blood during transplantation and related procedures in patients. I characterised the highly conserved decrease in the ATP/ADP ratios and the depletion of the adenosine nucleotide pools in various ischaemic tissues in a number of species over time under different temperatures. This work indicated the important mitochondrial and metabolic changes that occur in organs during storage and reperfusion in the recipient. I then used this knowledge to develop an Abstract improved mouse cardiomyocyte model for the assessment of IRI in vitro. For this, I utilised primary adult murine cardiomyocytes to demonstrate succinate accumulation during ischaemia as the metabolic factor that leads to mitochondrial ROS production during IRI. This led on to an exploration of potential drugs targeted to inhibit complex II as a possible therapy. Furthermore, I investigated the release and efflux of accumulated succinate and the mitochondrial damage associated molecular patterns (mtDAMPs) mtDNA upon reperfusion in this cell model. This was compared with the role of circulating mtDNA in mice undergoing transplantation and also in patients during liver transplant surgery. Hence, I could determine a time course of mtDNA release from mitochondria into the cytosol, as well as from cells into the circulation. Furthermore, I could show that the release of mtDNA was enhanced by opening of the mitochondrial permeability transition pore (MPTP), and that this could be inhibited using the MPTP inhibitor cyclosporin A. Overall, this work has generated new insights into the contribution of mitochondrial dysfunction to IRI during organ transplantation and has contributed to the development of potential therapies to ameliorate this damage.