ArticlePloS one2016
AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Neuroprotection through adiponectin receptor agonist: an updated meta-analysis of preclinical Alzheimer's disease studies.BMC neurology · 2025Pooled it
- Bridging tradition and modernity: mitochondrial dynamics as a Traditional Chinese Medicine therapeutic target in cardiovascular disease.Chinese medicine · 2026Review
- TAT-PBX1 fusion protein alleviates LPS-induced acute lung injury via AMPK-TFAM signaling activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Mitochondrial dynamics in diabetic peripheral neuropathy: Pathogenesis, progression, and therapeutic approaches.Medicine · 2025Review
- Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activation.Scientific reports · 2025Article
- The Balance of MFN2 and OPA1 in Mitochondrial Dynamics, Cellular Homeostasis, and Disease.Biomolecules · 2025Review
- Cardioprotection Through Pharmacological Activation of Sirtuin 5 in a Murine Model of Acute Myocardial Infarction.Drug design, development and therapy · 2025Article
- Regulatory mechanism and therapeutic potentials of naringin against inflammatory disorders.Heliyon · 2024Review
- Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis.Cell death and differentiation · 2024Article
- Overexpression of AMPKγ2 increases AMPK signaling to augment human T cell metabolism and function.The Journal of biological chemistry · 2024Article
- MDTR: a knowledge-guided interpretable representation for quantifying liver toxicity at transcriptomic level.Frontiers in pharmacology · 2024Article
- Article
- Differentiated modulation of signaling molecules AMPK and SIRT1 in experimentally drug-induced hepatocyte injury.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2023Article
- Review
- A Peptide HEPFYGNEGALR fromMolecules (Basel, Switzerland) · 2022Article
- Article
- Naringin regulates mitochondrial dynamics to protect against acetaminophen-induced hepatotoxicity by activating the AMPK/Nrf2 signaling pathway in vitro.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2022Article
- Collagen Sandwich Culture of Primary Hepatocytes for Image-Based Investigations.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The Imbalance of Mitochondrial Fusion/Fission Drives High-Glucose-Induced Vascular Injury.Biomolecules · 2021Article
- Mitochondrial stress response in drug-induced liver injury.Molecular biology reports · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury.
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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.