Ischemia/reperfusion(I/R)injury inevitably occurs during liver resection and transplantation.Elderly patients poorly recover from these surgeries.This reduced reparative capacity with aging is causatively associated w...Ischemia/reperfusion(I/R)injury inevitably occurs during liver resection and transplantation.Elderly patients poorly recover from these surgeries.This reduced reparative capacity with aging is causatively associated with decreased mitochondrial function after reperfusion.Mitochondrial autophagy(mitophagy)is a vital cellular process that timely clears abnormal and dysfunctional mitochondria.Impaired or insufficient autophagy can contribute to hepatocyte death after I/R.This review describes our current understanding of I/R injury and highlights new mechanistic correlation between sirtuin 1(SIRT1),mitofusin 2(MFN2),and autophagy in the pathogenesis of age-dependent hypersensitivity to reperfusion injury.The deacetylation of MFN2 by SIRT1 plays a pivotal role in the recovery from reperfusion injury by modulating the onset of autophagy.Targeting the SIRT1-MFN2 axis could be a new therapeutic target to reduce I/R injury in aged livers.展开更多
基金This work was supported by the USA National Institutes Health(NIH)grants R01 DK079878 and R01 DK09011504.
文摘Ischemia/reperfusion(I/R)injury inevitably occurs during liver resection and transplantation.Elderly patients poorly recover from these surgeries.This reduced reparative capacity with aging is causatively associated with decreased mitochondrial function after reperfusion.Mitochondrial autophagy(mitophagy)is a vital cellular process that timely clears abnormal and dysfunctional mitochondria.Impaired or insufficient autophagy can contribute to hepatocyte death after I/R.This review describes our current understanding of I/R injury and highlights new mechanistic correlation between sirtuin 1(SIRT1),mitofusin 2(MFN2),and autophagy in the pathogenesis of age-dependent hypersensitivity to reperfusion injury.The deacetylation of MFN2 by SIRT1 plays a pivotal role in the recovery from reperfusion injury by modulating the onset of autophagy.Targeting the SIRT1-MFN2 axis could be a new therapeutic target to reduce I/R injury in aged livers.
