ArticleJournal of hepatology2015
Sab (Sh3bp5) dependence of JNK mediated inhibition of mitochondrial respiration in palmitic acid induced hepatocyte lipotoxicity.
Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 138 citations in OpenAlex.
- Palmitic Acid Inhibits the Proliferation and Hypertrophy of Antler Chondrocytes by Disrupting Mitochondria-Associated Endoplasmic Reticulum Membrane Function.Antioxidants (Basel, Switzerland) · 2026Article
- A Global Perspective on Metabolic Dysfunction-Associated Steatotic Liver Disease: From Molecular Mechanisms to Therapeutic Strategy Innovation.Nutrients · 2026Review
- Mitochondrial dysfunction in hepatocellular carcinoma: from metabolism to targeted therapies.Molecular and cellular biochemistry · 2025Review
- Hesperetin Protects from Palmitic-Acid-Induced Lipotoxicity through the Inhibition of Glutaminolysis, mTORC1 Signaling, and Limited Apoptosis.Journal of agricultural and food chemistry · 2025Article
- Liver immunology: Biological role and clinical significance.World journal of hepatology · 2025Review
- Investigation of molecular mechanisms in silver nanoparticle-induced cytotoxicity from gene to metabolite level.Scientific reports · 2025Article
- At the Crossroads of Health and Disease: Consequences of Fat in the Liver.Annual review of physiology · 2025Review
- Jiangzhi Granule Ameliorates JNK-Mediated Mitochondrial Dysfunction to Reduce Lipotoxic Liver Injury in NASH.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Proteomics reveals periodontitis-driven oxidative stress and lipid metabolism disruption in NAFLD.Frontiers in endocrinology · 2025Article
- The immunoregulatory effects of scoparone on immune-mediated inflammatory diseases.Frontiers in immunology · 2025Review
- Imeglimin Halts Liver Damage by Improving Mitochondrial Dysfunction in a Nondiabetic Male Mouse Model of Metabolic Dysfunction-Associated Steatohepatitis.Antioxidants (Basel, Switzerland) · 2024Article
- Suppression of JNK pathway protects neurons from oxidative injury via attenuating parthanatos in glutamate-treated HT22 neurons.Scientific reports · 2024Article
- Updated mechanisms of MASLD pathogenesis.Lipids in health and disease · 2024Review
- Lipotoxicity, ER Stress, and Cardiovascular Disease: Current Understanding and Future Directions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- GDF15: Immunomodulatory Role in Hepatocellular Carcinoma Pathogenesis and Therapeutic Implications.Journal of hepatocellular carcinoma · 2024Review
- Mitochondrial P-JNK target, SAB (SH3BP5), in regulation of cell death.Frontiers in cell and developmental biology · 2024Review
- The Coumarin-Derivative Esculetin Protects against Lipotoxicity in Primary Rat Hepatocytes via Attenuating JNK-Mediated Oxidative Stress and Attenuates Free Fatty Acid-Induced Lipid Accumulation.Antioxidants (Basel, Switzerland) · 2023Article
- Hepatic SPARC Expression Is Associated with Inflammasome Activation during the Progression of Non-Alcoholic Fatty Liver Disease in Both Mice and Morbidly Obese Patients.International journal of molecular sciences · 2023Article
- Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis.Nature reviews. Gastroenterology & hepatology · 2023Review
- Exercise activates Sirt1-mediated Drp1 acetylation and inhibits hepatocyte apoptosis to improve nonalcoholic fatty liver disease.Lipids in health and disease · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsSustained c-Jun N-terminal kinase (JNK) activation by saturated fatty acids plays a role in lipotoxicity and the pathogenesis of non-alcoholic steatohepatitis (NASH). We have reported that the interaction of JNK with mitochondrial Sab leads to inhibition of respiration, increased reactive oxygen species (ROS), cell death and hepatotoxicity. We tested whether this pathway underlies palmitic acid (PA)-induced lipotoxicity in hepatocytes.
methodsPrimary mouse hepatocytes (PMH) from adeno-shlacZ or adeno-shSab treated mice and HuH7 cells were used.
resultsIn PMH, PA dose-dependently up to 1mM stimulated oxygen consumption rate (OCR) due to mitochondrial β-oxidation. At ⩾1.5mM, PA gradually reduced OCR, followed by cell death. Inhibition of JNK, caspases or treatment with antioxidant butylated hydroxyanisole (BHA) protected PMH against cell death. Sab knockdown or a membrane permeable Sab blocking peptide prevented PA-induced mitochondrial impairment, but inhibited only the late phase of both JNK activation (beyond 4h) and cell death. In PMH, PA increased p-PERK and its downstream target CHOP, but failed to activate the IRE-1α arm of the UPR. However, Sab silencing did not affect PA-induced PERK activation. Conversely, specific inhibition of PERK prevented JNK activation and cell death, indicating a major role upstream of JNK activation.
conclusionsThe effect of p-JNK on mitochondria plays a key role in PA-mediated lipotoxicity. The interplay of p-JNK with mitochondrial Sab leads to impaired respiration, ROS production, sustained JNK activation, and apoptosis.
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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.