Mitochondrial Damage and Mitophagy in Ischemia/Reperfusion-Induced Liver Injury

Abstract

The liver is innately vulnerable to hypoxia and anoxia. Ischemia/reperfusion (I/R) injury is a major obstacle in liver resection and transplantation. However, therapeutic strategies to attenuate reperfusion injury remain disappointing largely due to the complex and multifactorial nature of I/R injury. One key mechanism contributing to I/R injury in the liver is the onset of mitochondrial permeability transition and subsequent mitochondrial dysfunction. Mitochondrial integrity is critical for hepatocyte survival and function after I/R. Key quality control machinery in mitochondria is mitophagy that clears damaged or abnormal mitochondria in a timely manner. Evidence is accumulating to indicate that defective mitophagy is an important factor culminating in I/R injury. Here, we highlight our current knowledge on mitochondrial dysfunction after I/R in the liver, role of mitophagy in reperfusion injury, and therapeutic potential of mitophagy. We also discuss mitochondrial dysfunction in aged and fatty livers and their sensitivity to I/R injury and describe the various therapeutic approaches that have been proposed to ameliorate injury.