Recent insights into mitochondrial targeting strategies in liver transplantation

Abstract

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: Ischemia/reperfusion injury; Liver preservation solution; Liver transplantation; Mitochondria; Pharmacological conditioning.

Figure 1

Schematic timeline of the liver transplantation phases of I/R injury.

Figure 2

I/R injury caused by cold ischemia and warm ischemia can produce common and specific effects on various subsets of cells. For example, sinusoidal endothelial cells are more susceptible than hepatic parenchymal cells to the effects of cold preservation, and the reperfusion phase amplifies the ischemic injury with the preferential involvement of the hepatic parenchymal cells; A- space of Disse; B- sinusoid; C- sinusoidal endothelial cells (with fenestrae); D- biliary canaliculus; E- Stellate cell; F- Kupffer cell; H- hepatocyte; N- nucleus.

Figure 3

Mitochondrion-related processes and targets

Figure 4

Interaction between the regulation of gene expression by RNA interference due to the presence of pre-mature (pre-miRNA) and mature (miRNA) microRNAs and the mitochondria system