Aging aggravates hepatic ischemia-reperfusion injury in mice by impairing mitophagy with the involvement of the EIF2α-parkin pathway.

ABSTRACT: Hepatic ischemia-reperfusion (I/R) injury fundamentally influences the performance of aged liver grafts. The significance of mitophagy in the age dependence of sensitivity to I/R injury remains poorly understood. Here, we show that aging aggravated hepatic I/R injury with decreased mitophagy in mice. The enhancement of mitophagy resulted in significant protection against hepatic I/R injury. Parkin, an E3 ubiquitin ligase, was found depleted by I/R in aged livers. In oxygen-glucose deprivation reperfusion (OGD-Rep.)-treated L02 cells, parkin silencing impaired mitophagy and aggravated cell damage through a relative large mitochondrial membrane potential transition. The phosphorylation of the endoplasmic reticulum stress response protein EIF2α, which was also reduced in the aged liver, induc

SUBMITTER: Li Y 

PROVIDER: S-EPMC6128434 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature