Mitochondrial Permeability Transition in Liver Ischemia and Reperfusion: Role of c-Jun

The mitochondrial permeability transition (MPT) mediates hepatic necrosis after ischemia and reperfusion (I/R). Here, we studied the role of c-Jun N-terminal kinase 2 (JNK2) inMPT-induced liver injury. Wildtype (WT) and JNK2 knockout (KO) mice underwent 70 % liver ischemia for 1 hr followed by reperfusion for 8 hr, after which hepatocyte injury and animal survival was assessed. Compared withWT, JNK2KOmice had 38 % less alanine transaminase release and 39 % less necrosis by histology. Survival out to 14 days was also greater in JNK2KOmice (57 % vs. 11%), and overall Kaplan-Meier survival was improved. No difference in apoptosis was observed. Intravital multiphoton microscopy of potential-indicating rhodamine 123 after reperfusion revealed depolarized mitochondria in 82 % of WT hepatocytes, which decreased to 43 % in JNK2 KO hepatocytes. In conclusion, JNK2 contributes to hepatocellular injury and death after I/R in association with increased mitochondrial dysfunction via the MPT