Loss of sirtuin 1 and mitofusin 2 contributes to enhanced ischemia/reperfusion injury in aged livers

Aging Cell
Sung Kook ChunJae-Sung Kim

Abstract

Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23-26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo. Primary hepatocytes isolated from each age group were also exposed to simulated in vitro I/R. Biochemical, genetic, and imaging analyses were performed to assess cell death, autophagy flux, mitophagy, and mitochondrial function. Compared to young mice, old livers showed accelerated liver injury following mild I/R. Reperfusion of old hepatocytes also showed necrosis, accompanied with defective autophagy, onset of the mitochondrial permeability transition, and mitochondrial dysfunction. Biochemical analysis indicated a near-complete loss of both SIRT1 and MFN2 after I/R in old hepatocytes, which did not occur in young cells. Overexpression of either SIRT1 or MFN2 alone in old he...Continue Reading

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Citations

May 10, 2019·Cancer Cell International·Shentong YuJing Zhang
Jun 4, 2019·Frontiers in Physiology·Mafalda Escobar-Henriques, Mariana Joaquim
Jul 19, 2020·Scientific Reports·Uwe ScheuermannAndrew S Barbas
Apr 5, 2020·Cells·Xiaowen MaWen-Xing Ding
Dec 5, 2020·Journal of Ethnopharmacology·Tingting LouXiangyan Li
Jan 7, 2021·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Huali XiangLinquan Wu
Aug 28, 2021·Cells·Joseph Flores-ToroJae-Sung Kim

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Methods Mentioned

BETA
confocal microscopy
Immunoprecipitation
immunoprecipitation assay
acetylation
GTPase
ubiquitination
transfection

Software Mentioned

ImageJ
SigmaPlot

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