Ischemic Postconditioning Reduces Hepatic Ischemia-reperfusion Injury By Activating PARK2-mediated Mitophagy

Ischemia reperfusion injury(IRI)is an unavoidable consequence of prolonged hepatic ischemia.Ischemic postconditioning(IPO)refers to a series of brief ischemia and reperfusion(I/R)cycles applied at the late phase of ischemia or onset of reperfusion following an ischemic event.IPO has been shown to have protective effects in hepatic IRI,and represents a promising clinical strategy against hepatic IRI,however,the underlying mechanisms have not been elucidated.Here we report that IPO protcets liver from IRI by maintaining acidosis during early reoxygenation and acidosis reinforces ischemia-reperfusion-induced mitophagy in partial hepatic ischemia rats.First,it was verified that ischemic postconditioning activated mitochondrial autophagy by maintaining the early acidity of reperfusion.Mitochondrial markers decreased significantly in the ischemic postconditioning group,and this decline was not due to the decrease in mitochondrial generation or the increase in the overall autophagy level of cells.Second,whether reversing acidosis or inhibition mitophagy can compromise the protective effect conferred by IPO on hepatic IRI.Furthermore,mitophagy and hepatic effect are abolished in Park2 knockdown rats,indicating that IPO-acidosis-induced mitophagy is facilitated by the recruitment of PARK2 to mitochondria.Taken together,we found that IPO protected liver from IRI by maintaining acidosis and then reinforcing PARK2-dependent mitophagy.