Blocking donor liver Pannexin 1 channels facilitates mitochondria protection during liver transplantation（3966）.

Abstract

Static cold storage (SCS) is the standard technique for organ preservation during transplantation, resulting in cold ischemic injury. Hypoxia can induce Panx1 channels open, leading to release of ATP. However, it is unknown whether Panx1 play a role in SCS. Our research demonstrates that livers from Panx1^-/- mice exhibited reduced ATP release, resulting in protected hepatocytes during preservation. The donor liver damage is decreased during SCS with blocking Panx1. Transmission electron microscopy revealed a decreased mitochondria-associated ER membranes (MAMs) and an improved mitochondria morphology. Mechanistically, Panx1 blockade upregulated the PI3K-AKT pathway and increased Bcl2 level to combat apoptosis during liver preservation. The data indicate that blocking Panx1 during preservation of the donor liver can effectively improve mitochondrial function, reducing cellular stress damage. Then cold ischemia and reperfusion-related injuries are obviously decreased in liver transplantation.