The c-Jun N-terminal kinase (JNK) pathway enhances graft injury after liver 
transplantation (LT). We hypothesized that the JNK2 isoform promotes graft 
injury via the mitochondrial permeability transition (MPT). Livers of C57BL/6J 
(wild-type, WT) and JNK2 knockout (KO) mice were transplanted into WT recipients 
after 30 h of cold storage in UW solution. Injury after implantation was 
assessed by serum ALT, histological necrosis, TUNEL, Caspase 3 activity, 30-day 
survival, and cytochrome c and 4-hydroxynonenal immunostaining. Multiphoton 
microscopy after LT monitored mitochondrial membrane potential in vivo. After 
LT, ALT increased three times more in WT compared to KO (p < 0.05). Necrosis and 
TUNEL were more than two times greater in WT than KO (p < 0.05). Immunostaining 
showed a >80% decrease of mitochondrial cytochrome c release in KO compared to 
WT (p < 0.01). Lipid peroxidation was similarly decreased. Every KO graft but 
one survived longer than all WT grafts (p < 0.05, Kaplan-Meier). After LT, 
depolarization of mitochondria occurred in 73% of WT hepatocytes, which 
decreased to 28% in KO (p < 0.05). In conclusion, donor JNK2 promotes injury 
after mouse LT via the MPT. MPT inhibition using specific JNK2 inhibitors may be 
useful in protecting grafts against adverse outcomes from ischemia/reperfusion 
injury.