ArticleHepatology (Baltimore, Md.)2018
Loss of PDK4 switches the hepatic NF-κB/TNF pathway from pro-survival to pro-apoptosis.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 92 citations in OpenAlex.
- GATM alleviates sepsis-induced acute kidney injury via PDK4-mediated glycolytic reprogramming in renal tubular epithelial cells.Cellular and molecular life sciences : CMLS · 2026Article
- RELA Ablation Contributes to Progression of Hepatocellular Carcinoma with TP53Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting pyruvate metabolism generates distinct CD8+ T cell responses to gammaherpesvirus and B lymphoma.JCI insight · 2025Article
- Targeting HDAC3 Suppresses Ferroptosis and Demyelination in White Matter Injury by Restoring PDK4-Mediated Iron Homeostasis.CNS neuroscience & therapeutics · 2025Article
- Alpha lipoic acid diminishes migration and invasion in hepatocellular carcinoma cells through an AMPK-p53 axis.Scientific reports · 2024Article
- A Novel Bifunctional Fusion Protein (Anti-IL-17A-sST2) Protects against Acute Liver Failure, Modulating the TLR4/MyD88 Pathway and NLRP3 Inflammasome Activation.Biomedicines · 2024Article
- Genetic Ablation of Pyruvate Dehydrogenase Kinase Isoform 4 Gene Enhances Recovery from Hyperoxic Lung Injury: Insights into Antioxidant and Inflammatory Mechanisms.Biomedicines · 2024Article
- Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease.Signal transduction and targeted therapy · 2024Article
- Development of novel liver-targeting glucocorticoid prodrugs.Medicine in drug discovery · 2024Article
- PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy.Nature metabolism · 2023Article
- Targeting PDK2 rescues stress-induced impaired brain energy metabolism.Molecular psychiatry · 2023Article
- Negative regulation of pro-apoptotic AMPK/JNK pathway by itaconate in mice with fulminant liver injury.Cell death & disease · 2023Article
- Dichloroacetic acid and rapamycin synergistically inhibit tumor progression.Journal of Zhejiang University. Science. B · 2023Article
- The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4.Diabetes & metabolism journal · 2023Review
- Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.Cell reports · 2023Article
- The mInternational journal of biological sciences · 2023Article
- Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.Journal of xenobiotics · 2022Review
- An ischemia-homing bioengineered nano-scavenger for specifically alleviating multiple pathogeneses in ischemic stroke.Journal of nanobiotechnology · 2022Article
- ALKBH5-mediated m6A modification of circCCDC134 facilitates cervical cancer metastasis by enhancing HIF1A transcription.Journal of experimental & clinical cancer research : CR · 2022Article
- MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
It has been established that nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) members promote survival by upregulating antiapoptotic genes and that genetic and pharmacological inhibition of NF-κB is required for tumor necrosis factor (TNF)-induced hepatocyte apoptosis. In this study, we demonstrate that this pro-survival pathway is switched to pro-apoptosis under pyruvate dehydrogenase kinase 4 (PDK4)-deficient conditions. PDK4-deficiency triggered hepatic apoptosis concomitantly with increased numbers of aberrant mitochondria, reactive oxygen species (ROS) production, sustained c-Jun N-terminal Kinase (JNK) activation, and reduction of glutathione (GSH). Interestingly, PDK4 retained p65 in cytoplasm via a direct protein-protein interaction. Disruption of PDK4-p65 association promoted p65 nuclear translocation. This, in turn, facilitated p65 binding to the TNF promoter to activate TNF-TNFR1 apoptotic pathway. Pdk4
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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.