ArticleThe Journal of biological chemistry2015
Chronic Deletion and Acute Knockdown of Parkin Have Differential Responses to Acetaminophen-induced Mitophagy and Liver Injury in Mice.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 99 citations in OpenAlex.
- 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
- Imidazole Alkaloids Epiisopilosine and Epiisopiloturine Attenuate Acetaminophen-Induced Liver Toxicity in Mice via Autophagy Modulation and Anti-Inflammatory Effects.Journal of biochemical and molecular toxicology · 2026Article
- Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.Journal of Zhejiang University. Science. B · 2025Review
- Hepatocyte cellular repressor of E1A-stimulated genes 1 protects against acetaminophen-induced liver injury by promoting autophagy.Acta pharmacologica Sinica · 2025Article
- DAPK3 is Essential for DBP-Induced Autophagy of Mouse Leydig Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanism and regulation of mitophagy in liver diseases: a review.Frontiers in cell and developmental biology · 2025Review
- The multiple mechanisms and modes of cell death after acetaminophen overdose.Exploration of digestive diseases · 2025Article
- Hepatocyte-Specific HuR Protects Against Acetaminophen-Induced Liver Injury in Mice.Journal of cellular and molecular medicine · 2024Article
- Article
- Mitochondrial dysfunction: A promising therapeutic target for liver diseases.Genes & diseases · 2024Review
- TSP50 Attenuates DSS-Induced Colitis by Regulating TGF-β Signaling Mediated Maintenance of Intestinal Mucosal Barrier Integrity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury.Annual review of pathology · 2024Review
- High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice.Acta pharmaceutica Sinica. B · 2024Article
- Loss of microRNA-21 protects against acetaminophen-induced hepatotoxicity in mice.Archives of toxicology · 2023Article
- Article
- Reduced mitophagy is an early feature of NAFLD and liver-specific PARKIN knockout hastens the onset of steatosis, inflammation and fibrosis.Scientific reports · 2023Article
- Reduced hepatocyte mitophagy is an early feature of NAFLD pathogenesis and hastens the onset of steatosis, inflammation and fibrosis.Research square · 2023Article
- Metabolic Rewiring toward Oxidative Phosphorylation Disrupts Intrinsic Resistance to Ferroptosis of the Colon Adenocarcinoma Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We previously demonstrated that pharmacological induction of autophagy protected against acetaminophen (APAP)-induced liver injury in mice by clearing damaged mitochondria. However, the mechanism for removal of mitochondria by autophagy is unknown. Parkin, an E3 ubiquitin ligase, has been shown to be required for mitophagy induction in cultured mammalian cells following mitochondrial depolarization, but its role in vivo is not clear. The purpose of this study was to investigate the role of Parkin-mediated mitophagy in protection against APAP-induced liver injury. We found that Parkin translocated to mitochondria in mouse livers after APAP treatment followed by mitochondrial protein ubiquitination and mitophagy induction. To our surprise, we found that mitophagy still occurred in Parkin knock-out (KO) mice after APAP treatment based on electron microscopy analysis and Western blot analysis for some mitochondrial proteins, and Parkin KO mice were protected against APAP-induced liver injury compared with wild type mice. Mechanistically, we found that Parkin KO mice had decreased activated c-Jun N-terminal kinase (JNK), increased induction of myeloid leukemia cell differentiation protein (Mcl-1) expression, and increased hepatocyte proliferation after APAP treatment in their livers compared with WT mice. In contrast to chronic deletion of Parkin, acute knockdown of Parkin in mouse livers using adenovirus shRNA reduced mitophagy and Mcl-1 expression but increased JNK activation after APAP administration, which exacerbated APAP-induced liver injury. Therefore, chronic deletion (KO) and acute knockdown of Parkin have differential responses to APAP-induced mitophagy and liver injury in mice.
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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.