2018
DOI: 10.18632/aging.101511
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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-… Show more

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Cited by 16 publications
(17 citation statements)
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(50 reference statements)
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“…These findings were further extended through analyzing expression of the mitophagy adaptors Parkin, Beclin1, and Atg5. Consistent with previous studies, 34 sI/R treatment reduced the expression of Parkin, Beclin1, and Atg5 ( Figures 3 H–3K). Interestingly, SERCA overexpression upregulated their expressions ( Figures 3 H–3K), suggesting that SERCA levels are associated with mitophagy activity in CMECs under sI/R injury.…”
Section: Resultssupporting
confidence: 93%
“…These findings were further extended through analyzing expression of the mitophagy adaptors Parkin, Beclin1, and Atg5. Consistent with previous studies, 34 sI/R treatment reduced the expression of Parkin, Beclin1, and Atg5 ( Figures 3 H–3K). Interestingly, SERCA overexpression upregulated their expressions ( Figures 3 H–3K), suggesting that SERCA levels are associated with mitophagy activity in CMECs under sI/R injury.…”
Section: Resultssupporting
confidence: 93%
“…Impaired mitophagy triggers hepatic NLRP3 inflammasome activation, which contributes to the progression from simple steatosis to steatohepatitis [ 73 ]. Aging aggravates hepatic ischemia-reperfusion injury in mice by impairing mitophagy function via insufficient parkin expression [ 74 ]. Moreover, defects in mitophagy due to lysosomal cholesterol accumulation increased the susceptibility to hepatotoxicity induced by acetaminophen overdose [ 75 ].…”
Section: Discussionmentioning
confidence: 99%
“…Although the basal autophagy level is comparable in young and aged mice, the aged mice fail to remove damaged mitochondria after hepatic IR, showing defective SIRT1/Mfn2 mediated-mitophagy in the liver, which contributes to increased susceptibility to IR injury [171]. In human hepatic biopsy specimens, Parkin expression is negatively correlated with donor age and the peak level for aspartate aminotransferase is within the first week after liver transplantation, suggesting that PINK1/Parkin-mediated mitophagy is likely to be a protective mechanism in IR-induced injury [172]. In addition, alcoholic fatty liver may also be susceptible to IR injury as alcohol feeding accelerates hepatic IR injury in C57BL/6 mice, which is associated with restricted mitophagy [173].…”
Section: Mitophagy In Liver Ischemia/reperfusion Injurymentioning
confidence: 99%