ArticleRedox biology2019
Double deletion of PINK1 and Parkin impairs hepatic mitophagy and exacerbates acetaminophen-induced liver injury in mice.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 124 citations in OpenAlex.
- Mitochondrial quality control in acute liver injury and its therapeutic implications (Review).Molecular medicine reports · 2026Review
- Pathophysiological mechanisms of cell death affecting graft survival in liver transplantation.World journal of transplantation · 2026Review
- Loss of Vacuole Membrane Protein 1 protects against acetaminophen-induced liver injury by modulating inflammation and hepatocyte proliferation.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Animal models accurately representing acute liver failure (Review).International journal of molecular medicine · 2026Review
- Understanding Liver and Digestive Diseases: A Paved Road to Improve Diagnosis, Management, and Treatment.Exploration of digestive diseases · 2026Article
- Autophagy in the liver.Autophagy reports · 2026Review
- Mitochondria-driven inflammation: a new frontier in ovarian ageing.Journal of translational medicine · 2025Review
- Non-Invasive Redox Biomarkers Detected in Organ Preservation Outflow Solution Enable Early Prediction of Human Liver Allograft Dysfunction.Antioxidants (Basel, Switzerland) · 2025Article
- Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.Journal of Zhejiang University. Science. B · 2025Review
- Mitochondrial proteins as biomarkers of cellular senescence and age-associated diseases.Aging · 2025Review
- Induction of mitochondrial damage via the CREB3L1/miR-34c/COX1 axis by porcine epidemic diarrhea virus infection facilitates pathogenicity.Journal of virology · 2025Article
- Enhanced Parkin-mediated mitophagy mitigates adverse left ventricular remodelling after myocardial infarction: role of PR-364.European heart journal · 2025Article
- Mechanism and regulation of mitophagy in liver diseases: a review.Frontiers in cell and developmental biology · 2025Review
- Preserving mitochondrial homeostasis protects against drug-induced liver injury via inducing OPTN (optineurin)-dependent Mitophagy.Autophagy · 2024Article
- Investigating the interplay between mitophagy and diabetic neuropathy: Uncovering the hidden secrets of the disease pathology.Pharmacological research · 2024Review
- Article
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- FGF21-mediated autophagy: Remodeling the homeostasis in response to stress in liver diseases.Genes & diseases · 2024Review
- Comparative effects of 3,5-diiodo-L-thyronine and 3,5,3'-triiodo-L-thyronine on mitochondrial damage and cGAS/STING-driven inflammation in liver of hypothyroid rats.Frontiers in endocrinology · 2024Article
- Functional foods and bioactive compounds: a comprehensive review on their role in mitigating drug-induced liver injury.Frontiers in nutrition · 2024Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
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 survival after treatment with APAP although the serum levels of ALT were not significantly different among PINK1 KO, Parkin KO and WT mice. We only found mild defects of mitophagy in PINK1 KO or Parkin KO mice after APAP, and improved survival in PINK1 KO and Parkin KO mice could be due to other functions of PINK1 and Parkin independent of mitophagy. In contrast, APAP-induced mitophagy was significantly impaired in PINK1-Parkin DKO mice. PINK1-Parkin DKO mice had further elevated serum levels of ALT and increased mortality after APAP administration. In conclusion, our results demonstrated that PINK1-Parkin signaling pathway plays a critical role in APAP-induced mitophagy and liver injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.