1. Department of Surgery, Instituto Português de Oncologia de Coimbra, Coimbra, Portugal
2. Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal; and Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal
3. Unidade de Transplantação Hepática de Crianças e Adultos, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
4. Department of Surgery A, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Clínica Universitária de Cirurgia III, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; and Center for Investigation on Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
Ischemia/reperfusion (I/R) injury in liver transplantation can disrupt the normal activity of mitochondria in the hepatic parenchyma. This potential dysfunction of mitochondria after I/R injury could be responsible for the initial poor graft function or primary nonfunction observed after liver transplantation. Thus, determining the mechanisms that lead to human hepatic mitochondrial dysfunction might contribute to improving the outcome of liver transplantation. Furthermore, early identification of novel prognostic factors involved in I/R injury could serve as a key endpoint to predict the outcome of liver grafts and also to promote the early adoption of novel strategies that protect against I/R injury. Here, we briefly review recent advances in the study of mitochondrial dysfunction and I/R injury, particularly in relation to liver transplantation. Next, we highlight various pharmacological therapeutic strategies that could be applied, and discuss their relationship to relevant mitochondrion-related processes and targets. Lastly, we note that although considerable progress has been made in our understanding of I/R injury and mitochondrial dysfunction, further investigation is required to elucidate the cellular and molecular mechanisms underlying these processes, thereby identifying biomarkers that can help in evaluating donor organs.
Keywords: Liver transplantation, Mitochondria, Ischemia/reperfusion injury, Liver preservation solution, Pharmacological conditioning