Early Stage Functions of Mitochondrial Autophagy and Oxidative Stress in Acetaminophen-Induced Liver Injury.

Research paper by Yan Y Gao, Shifeng S Chu, Zhao Z Zhang, Wei W Zuo, Congyuan C Xia, Qidi Q Ai, Piao P Luo, Peng P Cao, Naihong N Chen

Indexed on: 20 Nov '16Published on: 20 Nov '16Published in: Journal of Cellular Biochemistry


Mitochondria go through frequent cycles of fusion and fission, a process required for mitochondrial quality control by eliminating ROS-damaged mitochondria through mitochondrial autophagy. Acetaminophen (APAP) overdose can cause liver injury in animals and human beings by inducing mitochondrial damage, which need to be further evaluated. The aim of the current study is to assess the changes between oxidative damage and mitophagy in vivo and in vitro, which mimics APAP-induced liver injury (AILI) in humans. Liver damage was monitored by measuring the levels of biochemical indexes. Proteins associated with oxidative stress were inspected by western blot analysis. After given APAP to both Nrf2(-/-) and wild-type mice, Nrf2(-/-) mice were highly susceptible to APAP induced liver injury. Actually, rapamycin promoted the process of autophagy, reducing the formation of giant mitochondria and lipid droplets. Both tBHQ and NAC protected hepatic cells, promoting Nrf2 translocation into nucleus and increasing the expression of downstream enzymes and proteins. C57BL/6 mice with stabilized Nrf2 had increased hepatic up-regulation of Nrf2 and other antioxidant enzymes, and reduced the mitochondria dysfunction. Interestingly, APAP-induced mitochondrial changes of Drp1; however, the initiation of mitochondria fission was inhibited by MDIVI-1, causing much more serious hepatic impairment. In the early stage of AILI, Nrf2 played a protective role in antioxidant activity while mitophagy protected against oxidative stress damage by the scavenging function. Promoting that both Drp1 and Nrf2 could be a promising new approach to reduce AILI. This article is protected by copyright. All rights reserved.

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