Double deletion of PINK1 and Parkin impairs hepatic mitophagy and exacerbates acetaminophen-induced liver injury in mice

Redox Biology
Hua WangWen-Xing Ding

Abstract

Mitochondria damage plays a critical role in acetaminophen (APAP)-induced necrosis and liver injury. Cells can adapt and protect themselves by removing damaged mitochondria via mitophagy. PINK1-Parkin pathway is one of the major pathways that regulate mitophagy but its role in APAP-induced liver injury is still elusive. We investigated the role of PINK1-Parkin pathway in hepatocyte mitophagy in APAP-induced liver injury in mice. Wild-type (WT), PINK1 knockout (KO), Parkin KO, and PINK1 and Parkin double KO (DKO) mice were treated with APAP for different time points. Liver injury was determined by measuring serum alanine aminotransferase (ALT) activity, H&E staining as well as TUNEL staining of liver tissues. Tandem fluorescent-tagged inner mitochondrial membrane protein Cox8 (Cox8-GFP-mCherry) can be used to monitor mitophagy based on different pH stability of GFP and mCherry fluorescent proteins. We overexpressed Cox8-GFP-mCherry in mouse livers via tail vein injection of an adenovirus Cox8-GFP-mCherry. Mitophagy was assessed by confocal microscopy for Cox8-GFP-mCherry puncta, electron microscopy (EM) analysis for mitophagosomes and western blot analysis for mitochondrial proteins. Parkin KO and PINK1 KO mice improved the surv...Continue Reading

Citations

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Jun 13, 2020·Archives of Toxicology·Qiuhua TanZhengquan Su
Oct 28, 2019·Frontiers in Pharmacology·Zuqing SuGuangjuan Zheng
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Aug 9, 2020·Frontiers in Cell and Developmental Biology·Ming YangLin Sun
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Methods Mentioned

BETA
ubiquitination
electron
confocal microscopy
electron microscopy
protein assay
PCR
genotyping
fluorescence microscopy
transgenic

Software Mentioned

MetaMorph
SPOT Imaging
SPOT

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