ArticleJournal of lipid research2014
Arachidonic acid downregulates acyl-CoA synthetase 4 expression by promoting its ubiquitination and proteasomal degradation.
Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 71 citations in OpenAlex.
- Ferroptosis: The Demise of Cells Through Phospholipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- YTHDF2 regulates ACSL4-dependent ferroptosis of keratinocytes in diabetic wound healing.Clinical science (London, England : 1979) · 2025Article
- Chikungunya Replication and Infection Is Dependent upon and Alters Cellular Hexosylceramide Levels in Vero Cells.Viruses · 2025Article
- Research progress of ferroptosis pathway and its related molecular ubiquitination modification in liver cancer.Frontiers in oncology · 2025Review
- Histone lactylation exacerbates acute lung injury in septic mice by promoting ferroptosis in pulmonary microvascular endothelial cells.Burns & trauma · 2025Article
- TCP1 expression alters the ferroptosis sensitivity of diffuse large B-cell lymphoma subtypes by stabilising ACSL4 and influences patient prognosis.Cell death & disease · 2024Article
- Ferroptosis: principles and significance in health and disease.Journal of hematology & oncology · 2024Review
- Autophagy Regulates Ferroptosis-Mediated Diabetic Liver Injury by Modulating the Degradation of ACSL4.Journal of diabetes research · 2024Article
- Review
- Enhancing Hepatic MBOAT7 Expression in Mice With Nonalcoholic Steatohepatitis.Gastro hep advances · 2023Article
- Iron accumulation and lipid peroxidation: implication of ferroptosis in hepatocellular carcinoma.Frontiers in endocrinology · 2023Review
- Article
- Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion.Signal transduction and targeted therapy · 2022Article
- Genetic Alteration, Prognostic and Immunological Role of Acyl-CoA Synthetase Long-Chain Family Member 4 in a Pan-Cancer Analysis.Frontiers in genetics · 2022Article
- Ferroptosis: machinery and regulation.Autophagy · 2021Review
- High-fat diet impairs ferroptosis and promotes cancer invasiveness via downregulating tumor suppressor ACSL4 in lung adenocarcinoma.Biology direct · 2021Article
- Regulation of Ferroptosis Pathway by Ubiquitination.Frontiers in cell and developmental biology · 2021Review
- Inhibition of Acyl-CoA Synthetase Long-Chain Family Member 4 Facilitates Neurological Recovery After Stroke by Regulation Ferroptosis.Frontiers in cellular neuroscience · 2021Article
- The skeletal muscles of mice infected with Plasmodium berghei and Plasmodium chabaudi reveal a crosstalk between lipid mediators and gene expression.Malaria journal · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
ACSL4 is a member of the long-chain acyl-CoA synthetase (ACSL) family with a marked preference for arachidonic acid (AA) as its substrate. Although an association between elevated levels of ACSL4 and hepatosteatosis has been reported, the function of ACSL4 in hepatic FA metabolism and the regulation of its functional expression in the liver remain poorly defined. Here we provide evidence that AA selectively downregulates ACSL4 protein expression in hepatic cells. AA treatment decreased the half-life of ACSL4 protein in HepG2 cells by approximately 4-fold (from 17.3 ± 1.8 h to 4.2 ± 0.4 h) without causing apoptosis. The inhibitory action of AA on ACSL4 protein stability could not be prevented by rosiglitazone or inhibitors that interfere with the cellular pathways involved in AA metabolism to biologically active compounds. In contrast, treatment of cells with inhibitors specific for the proteasomal degradation pathway largely prevented the AA-induced ACSL4 degradation. We further show that ACSL4 is intrinsically ubiquitinated and that AA treatment can enhance its ubiquitination. Collectively, our studies have identified a novel substrate-induced posttranslational regulatory mechanism by which AA downregulates ACSL4 protein expression in hepatic cells.
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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.