Affinage

PDK4

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial · UniProt Q16654

Length
411 aa
Mass
46.5 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDK4 is a mitochondrial serine/threonine kinase that phosphorylates the E1alpha subunit of the pyruvate dehydrogenase complex (PDC), inhibiting PDC activity to suppress pyruvate oxidation and redirect metabolic flux from carbohydrate toward fatty acid utilization (PMID:8798399, PMID:31351920). This switch underlies physiological fuel selection across tissues, being induced by high-fat feeding in skeletal muscle, during hibernation, and during late pregnancy and progesterone signaling in the heart, and it reprograms cellular metabolism toward glycolysis or fatty acid oxidation in numerous disease and developmental contexts (PMID:10905486, PMID:11842126, PMID:28928113). PDK4 transcription integrates a broad set of upstream signals: it is induced by E2F1, FOXO1, thyroid hormone receptor with PGC-1alpha and C/EBPbeta coactivation, FXR, and the CD36/FoxO1/PPARdelta fatty-acid-sensing axis, repressed by insulin via Akt-FOXO1 and by ErbB2/Erk signaling, and silenced epigenetically by G9a-mediated H3K9 methylation; its mRNA is additionally controlled post-transcriptionally by m6A modification read by YTHDF1/eEF2 and IGF2BP3 (PMID:15026305, PMID:18308721, PMID:18667418, PMID:19948729, PMID:21852536, PMID:21586575, PMID:26728993, PMID:32444598, PMID:27217333, PMID:16873695). Beyond PDC inhibition, PDK4 has non-canonical activities: it phosphorylates SEPT2 to recruit DRP1 and drive mitochondrial fission (PMID:35969774), phosphorylates HDAC8 at Ser-39 to suppress CD20 (PMID:39004737), binds and stabilizes CREB to activate mTORC1 via RHEB (PMID:25164809), retains NF-kB p65 in the cytoplasm to restrain TNF-driven apoptosis (PMID:29603325), and interacts with SIRT1 to promote glycolysis (PMID:39080028). Through these activities PDK4 controls cell survival, ferroptosis resistance, the senescence-associated secretory phenotype, tumor growth, cardiac metabolic remodeling, and vascular calcification (PMID:29603325, PMID:33626342, PMID:37903887, PMID:33203874). A splice-site deletion in PDK4 is genetically associated with familial dilated cardiomyopathy in Doberman Pinscher dogs (PMID:22447147).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Established PDK4 as a distinct PDH kinase isoenzyme with intrinsic enzymatic activity, answering what the gene product does at the biochemical level.

    Evidence Positional cloning and biochemical activity assay of recombinant PDK4 on PDC E1alpha

    PMID:8798399

    Open questions at the time
    • Did not define isoform-specific regulatory or tissue-distribution features
    • No structural basis for substrate selectivity
  2. 2002 Medium

    Showed PDK4 is the physiological effector of carbohydrate-to-fat fuel switching, linking its induction to whole-body metabolic adaptation.

    Evidence Isoform-specific Western blot and PDK activity assays in high-fat-fed muscle and across hibernation states in multiple tissues

    PMID:10905486 PMID:11842126

    Open questions at the time
    • Correlative induction without genetic loss-of-function in these models
    • Did not resolve transcriptional drivers
  3. 2008 High

    Defined the transcriptional control logic of PDK4, showing it is a direct target of E2F1 and of fatty-acid sensing through CD36/FoxO1/PPARdelta.

    Evidence ChIP, promoter mutagenesis, E2F1 KO mice, and reciprocal CD36 gain/loss-of-function in vitro and in CD36-null and PPARdelta-null mice

    PMID:18308721 PMID:18667418

    Open questions at the time
    • Did not integrate the relative contribution of each input in a single tissue
    • Combinatorial regulation among factors not mapped
  4. 2009 High

    Extended the transcriptional network to hormonal and stress inputs, establishing TRbeta/PGC-1alpha, C/EBPbeta, p38/PPARgamma, and insulin/Akt-FOXO1 as PDK4 regulators.

    Evidence ChIP, binding-site mutagenesis, siRNA knockdown in hepatocytes, pharmacological pathway dissection in adipose, and hyperinsulinemic clamps with Akt/FOXO1 readouts

    PMID:15026305 PMID:16873695 PMID:19948729 PMID:20739620 PMID:21586575

    Open questions at the time
    • Cross-talk and hierarchy among coactivators not resolved
    • Mostly rodent tissue, human regulation less defined
  5. 2011 High

    Placed PDK4 as a metabolic node downstream of oncogenic and adhesion signaling, where its suppression sustains PDH flux and proliferation.

    Evidence ErbB2/Erk manipulation with PDK4 gain-of-function, metabolic flux, lipogenesis, and proliferation assays in ECM-attached/detached cells

    PMID:21852536

    Open questions at the time
    • Did not establish whether PDK4 acts solely via PDC here
    • In vivo tumor relevance not tested in this study
  6. 2012 High

    Demonstrated that PDK4 induction drives pathological cardiac metabolic remodeling and dysfunction, validated by PDK4 deletion and pharmacological inhibition.

    Evidence FOXO1-driven PDK4 in RV hypertrophy with DCA reversal; PDK4 KO rescue of ANG II diastolic dysfunction with ex vivo flux; Doberman GWAS linking a PDK4 splice variant to dilated cardiomyopathy

    PMID:22447147 PMID:23247844 PMID:23396452

    Open questions at the time
    • Mechanism connecting the canine splice variant to disease at protein level unresolved
    • Tissue-specific contribution versus systemic effects not separated
  7. 2014 Medium

    Uncovered the first non-canonical PDK4 function — a kinase-independent scaffolding role stabilizing CREB to drive RHEB/mTORC1 signaling.

    Evidence Co-IP, CREB stability and RHEB expression assays, mTORC1 activity, and xenograft tumor models

    PMID:25164809

    Open questions at the time
    • Single-lab Co-IP without reciprocal structural mapping
    • Whether this requires PDK4 catalytic activity not resolved
  8. 2017 High

    Established PDK4 as the controlling switch between glycolysis and oxidative phosphorylation during cellular differentiation and progesterone-driven cardiac remodeling.

    Evidence Bidirectional PDK4 manipulation with lactate/ATP readouts in trophoblasts; 13C flux tracing with PDK4 blockade in pregnancy heart model

    PMID:28814762 PMID:28928113

    Open questions at the time
    • Upstream control beyond hCG/cAMP/PKA in trophoblast not fully mapped
    • Long-term physiological consequences not addressed
  9. 2018 High

    Revealed PDK4 as a survival and gluconeogenic regulator in liver via cytoplasmic p65 retention and an FAO/AMP/AMPK/CREB axis.

    Evidence PDK4-p65 Co-IP, KO mice, ChIP at TNF promoter, rescue by p65/TNFR1 inhibition; metabolic flux with etomoxir defining FAO-dependent AMPK/PDE4B/CREB signaling

    PMID:29603325 PMID:30065033

    Open questions at the time
    • Whether p65 retention is direct kinase activity or scaffolding unresolved
    • Tissue specificity of the apoptotic role not delineated
  10. 2020 High

    Defined post-transcriptional m6A control of PDK4 and broadened its disease roles into autophagy-dependent vascular calcification, stem cell fate, and liver regeneration.

    Evidence m6A-seq, YTHDF1/eEF2/IGF2BP3 and WTAP binding assays, dm6ACRISPR; PDK4 manipulation in VSMC autophagy, LKB1 epistasis in intestinal stem cells, and PDK4 KO hepatectomy models

    PMID:31930988 PMID:32258946 PMID:32444598 PMID:33203874 PMID:37154586

    Open questions at the time
    • Relative weight of transcriptional versus m6A control in vivo unclear
    • Whether non-canonical roles share a common molecular basis not addressed
  11. 2021 High

    Identified PDK4 as a dominant determinant of ferroptosis resistance, linking PDC inhibition to suppression of lipid-peroxidation substrate supply.

    Evidence Unbiased siRNA metabolic-enzyme screen, PDH activity and fatty acid synthesis assays, lipid peroxidation readouts, and high-fat diet mouse model in pancreatic carcinoma

    PMID:33626342

    Open questions at the time
    • Generality across other tumor types not tested here
    • Interaction with established ferroptosis machinery (GPX4) not mapped
  12. 2022 High

    Demonstrated a PDC-independent kinase function: PDK4 phosphorylates SEPT2 to recruit DRP1 and drive mitochondrial fission.

    Evidence Phosphoproteomic substrate screen, SEPT2 phosphomutants, DRP1 localization, and rescue of mitochondrial dynamics in mitofusin 2-deficient cells

    PMID:35969774

    Open questions at the time
    • Physiological contexts engaging this axis versus PDC inhibition not delineated
    • Structural basis of SEPT2 recognition unknown
  13. 2023 High

    Connected PDK4-driven glycolytic lactate to ROS-dependent senescence signaling, defining its role in the senescence-associated secretory phenotype.

    Evidence PDK4 knockdown/inhibition, lactate/ROS/NOX1 readouts, SASP measurement, and in vivo tumor and aging models

    PMID:37903887

    Open questions at the time
    • Whether the lactate-NOX1 link is direct not fully resolved
    • Therapeutic window of PDK4 inhibition in aging not defined
  14. 2024 Medium

    Expanded the non-canonical phosphorylation repertoire and partner interactions, with PDK4 phosphorylating HDAC8 to suppress CD20 and interacting with SIRT1 to promote glycolysis.

    Evidence HDAC8 Ser-39 phosphorylation with CD20 deacetylation in resistant DLBCL; SIRT1-PDK4 Co-IP with bidirectional PDK4 manipulation in decidualization

    PMID:39004737 PMID:39080028

    Open questions at the time
    • Single-lab studies without reciprocal structural validation
    • Whether nuclear PDK4 pool is functionally distinct from mitochondrial pool unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PDK4 partitions between its mitochondrial PDC-inhibitory role and its cytoplasmic/nuclear non-canonical activities, and what governs substrate choice among PDC, SEPT2, HDAC8, CREB, p65, and SIRT1.
  • No unifying model for localization-dependent function
  • No structural determinants of non-PDC substrate selection identified
  • Relative in vivo contribution of canonical versus non-canonical roles unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005739 mitochondrion 2 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1852241 Organelle biogenesis and maintenance 1 R-HSA-8953897 Cellular responses to stimuli 1
Partners
CREBDRP1HDAC8PDHA1RELASEPT2SIRT1

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 PDK4 encodes a fourth pyruvate dehydrogenase kinase isoenzyme that phosphorylates the E1alpha subunit of the mitochondrial pyruvate dehydrogenase complex (PDC), thereby inhibiting PDC activity and suppressing pyruvate oxidation. Biochemical analyses of recombinant PDK4 protein confirmed this enzymatic activity. Positional cloning, recombinant protein expression, biochemical activity assay The Journal of biological chemistry High 8798399
2000 High-fat feeding selectively upregulates PDK4 protein expression in slow-twitch (soleus) skeletal muscle, and this increased PDK4 expression is associated with markedly reduced sensitivity of PDK activity to inhibition by pyruvate, demonstrating that PDK4 isoform switching underlies altered regulatory characteristics of PDK in response to dietary fat. Western blot with isoform-specific antibodies, PDK activity assays with varying pyruvate concentrations, dietary intervention Diabetes Medium 10905486
2002 PDK4 mRNA and protein are coordinately upregulated across heart, skeletal muscle, and white adipose tissue during mammalian hibernation, coinciding with metabolic fuel switching from carbohydrate to fatty acid oxidation. PDK4 inhibits pyruvate dehydrogenase to minimize carbohydrate oxidation and allow fatty acid combustion. Quantitative mRNA analysis, Western blot, tissue-specific expression profiling across hibernation states Physiological genomics Medium 11842126
2004 Insulin suppresses PDK4 mRNA expression in rat skeletal muscle predominantly through insulin signaling rather than through reduction of plasma free fatty acids (FFA); Intralipid infusion to prevent FFA decline blocked only ~20% of insulin-mediated PDK4 suppression, establishing that insulin acts on PDK4 expression largely independent of circulating FFA. Euglycemic-hyperinsulinemic clamp, Intralipid infusion, quantitative RT-PCR, Western blot in rat skeletal muscle American journal of physiology. Endocrinology and metabolism Medium 15026305
2008 CD36-mediated fatty acid uptake upregulates FoxO1 protein levels and activity in muscle cells, which in turn induces PDK4 expression to suppress glucose oxidation. CD36 knockdown blunts fasting induction of FoxO1 and PDK4 in vivo. This CD36-dependent regulation of FoxO1/PDK4 is mediated through the nuclear receptor PPARdelta/beta. CD36 overexpression/knockdown in C2C12 cells, in vivo fasting experiments with CD36-null and PPARdelta/beta-null mice, fatty acid flux manipulation The Journal of biological chemistry High 18308721
2008 E2F1 directly transcriptionally activates PDK4 gene expression by binding to two overlapping E2F binding sites in the PDK4 promoter. Rb inactivation induces PDK4 and enriches E2F1 occupancy at the PDK4 promoter. E2F1 enforced expression suppresses glucose oxidation in myoblasts, and E2F1 loss blunts PDK4 expression and improves myocardial glucose oxidation in vivo. Chromatin immunoprecipitation (ChIP), promoter transactivation assays with E2F site mutations, E2F1 KO mice, enforced E2F1 expression, Rb inactivation The Journal of biological chemistry High 18667418
2009 Thyroid hormone (T3) induces PDK4 gene expression through two thyroid hormone receptor beta binding sites in the rat PDK4 promoter. PGC-1alpha acts as a transcriptional coactivator in this regulation: T3 increases PGC-1alpha abundance and its association with the PDK4 promoter, and PGC-1alpha knockdown diminishes T3-mediated PDK4 induction. Promoter binding site identification, ChIP, PGC-1alpha siRNA knockdown in primary rat hepatocytes, T3 administration to hypothyroid rats The Journal of biological chemistry High 19948729
2010 Epinephrine induces PDK4 mRNA expression in rat white adipose tissue through a p38 MAPK and PPARgamma-dependent pathway. Inhibition of p38 MAPK with SB202190 attenuates epinephrine-mediated PDK4 induction without affecting lipolysis, identifying p38 MAPK as a specific regulator of PDK4 in adipose tissue. Ex vivo/in vivo epinephrine treatment, p38 MAPK inhibitor SB202190, PPARgamma inhibitor, AMPK activators, quantitative mRNA analysis in rat adipose tissue American journal of physiology. Cell physiology Medium 20739620
2011 ErbB2/Erk signaling suppresses PDK4 expression to maintain pyruvate dehydrogenase (PDH) flux in ECM-attached cells. ECM detachment increases PDK4 expression in an Erk-dependent manner; overexpression of PDK4 in ECM-detached cells suppresses ErbB2-mediated ATP rescue and in attached cells decreases PDH flux, de novo lipogenesis, and cell proliferation. ErbB2 overexpression, EGF stimulation, Erk pathway manipulation, PDK4 overexpression, metabolic flux analysis, lipogenesis measurement, cell proliferation assays Genes & development High 21852536
2011 C/EBPbeta directly induces PDK4 gene expression through two C/EBPbeta binding sites in the Pdk4 promoter and reduces PDC activity. C/EBPbeta also participates in thyroid hormone (T3)-mediated PDK4 induction: T3 increases C/EBPbeta abundance, and C/EBPbeta siRNA knockdown diminishes T3 induction of PDK4. Promoter transactivation assays, C/EBPbeta binding site identification, siRNA knockdown in primary rat hepatocytes, PDC activity measurement The Journal of biological chemistry Medium 21586575
2012 FOXO1 upregulates PDK4 expression in right ventricular hypertrophy, causing increased glycolysis relative to glucose oxidation and impaired right ventricular function. Dichloroacetate (a PDK4 inhibitor) chronically decreases PDK4 and FOXO1 expression, activates PDH, restores glucose oxidation, and improves cardiac output. Microarray gene expression analysis, isolated working heart perfusion, PDK4/FOXO1 protein quantification, chronic dichloroacetate treatment in vivo, cardiac output measurement Journal of molecular medicine (Berlin, Germany) Medium 23247844
2012 A 16-base pair deletion in the 5' donor splice site of intron 10 of the PDK4 gene is genetically associated with familial dilated cardiomyopathy in Doberman Pinscher dogs. Affected dogs show mitochondrial ultrastructural abnormalities including megamitochondria and whorling. Genome-wide association study, fine-mapping, DNA sequencing, electron microscopy of myocardium Human genetics Medium 22447147
2013 Angiotensin II (ANG II) reduces cardiac glucose oxidation in part by increasing PDK4 levels and by promoting SIRT3-dependent acetylation of the pyruvate dehydrogenase (PDH) complex, reducing PDH activity. PDK4 deletion prevents ANG II-induced diastolic dysfunction and normalizes glucose oxidation to basal levels. Ex vivo heart perfusion with metabolic flux measurement, PDK4 KO mice, ANG II infusion model, PDH phosphorylation and acetylation measurements American journal of physiology. Heart and circulatory physiology High 23396452
2014 PDK4 protein physically binds to CREB and prevents its proteasomal degradation. Stabilized CREB then transcriptionally induces RHEB expression, which activates mTORC1 independently of AMPK or TSC2, promoting aerobic glycolysis and tumor growth. Co-immunoprecipitation, PDK4 overexpression/knockdown, CREB protein stability assay, RHEB expression analysis, mTORC1 activity measurement, xenograft tumor models The Journal of biological chemistry Medium 25164809
2015 ZBTB2 transcriptionally represses RelA/p65 expression by blocking Sp1 binding to the RelA/p65 promoter. Since RelA/p65 directly binds PGC-1alpha to decrease PDK4 transcription, ZBTB2-mediated p65 repression indirectly increases PDK4 expression, inhibits PDH, and shifts glucose metabolism toward glycolysis. Promoter reporter assays, Sp1 binding competition, ZBTB2 overexpression/knockdown, metabolite measurements (pyruvate, lactate), xenograft tumor models Nucleic acids research Medium 25609694
2016 miR-182 directly targets and suppresses PDK4 expression, thereby increasing PDH activity and promoting de novo lipogenesis from acetyl-CoA in lung cancer cells. This miR-182/PDK4 axis drives cancer cell growth partly through lipogenesis and downstream JNK-ROS signaling. miR-182 overexpression/knockdown, direct 3'UTR targeting validation, PDH activity assay, lipogenesis measurement with ACLY/FASN inhibitors, ROS and JNK pathway analysis Oncogene Medium 27641336
2016 Farnesoid X receptor (FXR) activation transcriptionally upregulates PDK4 as a target gene, which drives metabolic reprogramming toward aerobic glycolysis and accumulation of glycolytic intermediates to support cell proliferation during liver regeneration. FXR agonist treatment, PDK4 mRNA/protein measurement, metabolic profiling (lactate, pyruvate, glycine), liver regeneration mouse model, in vitro cell proliferation assays Scientific reports Medium 26728993
2017 PDK4 is the dominant PDK isoform in human cytotrophoblasts and its expression is substantially downregulated upon syncytialization via the hCG/cAMP/PKA signaling pathway. PDK4 knockdown reduces lactate and increases ATP, while PDK4 overexpression has opposite effects, demonstrating PDK4 controls the metabolic switch from glycolysis to oxidative phosphorylation during trophoblast differentiation. Primary human trophoblast culture, siRNA knockdown, PDK4 overexpression, lactate/ATP measurement, syncytialization assay, cAMP/PKA pathway manipulation Scientific reports Medium 28814762
2017 PDK4 inhibition with DCA results in increased PDH activity, reduced bladder cancer cell growth, and G0-G1 phase cell cycle arrest. siRNA knockdown of PDK4 also inhibits bladder cancer cell proliferation, and DCA combined with cisplatin reduces tumor volumes in xenograft models through intratumoral necrosis. DCA pharmacological inhibition, siRNA knockdown, PDH activity assay, cell cycle analysis, xenograft tumor model Molecular cancer therapeutics Medium 29907593
2018 Adropin stimulates cardiac cells through GPR19 (a putative adropin receptor) to activate the p44/42 MAPK pathway, which decreases PDK4 expression, reduces inhibitory PDH phosphorylation, and shifts mitochondrial fuel utilization toward glucose. GPR19 depletion alone increases PDK4 expression and reduces mitochondrial respiration. Adropin stimulation of H9c2 cardiac cells, GPR19 genetic depletion, MAPK pathway pharmacological inhibition, PDK4/PDH phosphorylation Western blot, mitochondrial respiration measurement Redox biology Medium 29909017
2018 PDK4 deficiency in hepatocytes triggers pro-apoptotic signaling by causing PDK4 to lose its cytoplasmic retention of the NF-kB subunit p65. PDK4 physically interacts with p65 to retain it in the cytoplasm; loss of PDK4 allows p65 nuclear translocation, which drives TNF promoter binding and activates the TNF-TNFR1 apoptotic pathway with sustained JNK activation and ROS production. Co-immunoprecipitation (PDK4-p65 interaction), PDK4 KO mice, p65 nuclear/cytoplasmic fractionation, ChIP at TNF promoter, JNK/ROS measurement, pharmacological p65 and TNFR1 inhibition rescue experiments Hepatology (Baltimore, Md.) High 29603325
2018 PDK4 deficiency decreases intracellular ATP levels (by reducing fatty acid oxidation), which activates AMPK, leading to phosphorylation of PDE4B. This reduces cAMP levels and consequently reduces phospho-CREB, suppressing glucagon-mediated gluconeogenic gene expression and hepatic glucose production. PDK4 KO and overexpression in hepatocytes, metabolic flux analysis (fatty acid oxidation), AMPK/PDE4B/cAMP/CREB pathway measurement, FAO inhibitor etomoxir, gluconeogenic gene expression Diabetes High 30065033
2019 PDK4 overexpression in myotube cultures is sufficient to promote myofiber shrinkage with enhanced protein catabolism and mitochondrial abnormalities. Blockade of PDK4 restores myotube size in cultures exposed to tumor-conditioned media, establishing a direct role for PDK4 in cancer cachexia-associated skeletal muscle atrophy. Viral-mediated PDK4 overexpression in myotube cultures, PDK4 blockade, myotube size measurement, protein catabolism assays, mitochondrial morphology analysis FASEB journal Medium 30894018
2019 PDK4 overexpression causes increased fatty acid oxidation in cancer cells, and upregulated PDK4 expression indicates an overarching metabolic shift toward fatty acid utilization as energy fuel. PPARα overexpression and TTA treatment increase both fatty acid oxidation and PDK4 expression, while PDK4 overexpression itself is sufficient to drive increased fatty acid oxidation. PPARα overexpression, TTA treatment, PDK4 overexpression in MDA-MB-231 and HeLa cells, fatty acid oxidation assay, Seahorse metabolic analysis Mitochondrion Medium 31351920
2020 m6A modification of the PDK4 5'UTR positively regulates PDK4 translation elongation via binding with the YTHDF1/eEF-2 complex, and mRNA stability via binding with IGF2BP3. TBP transcriptionally increases METTL3 expression in cervical cancer cells. Targeted demethylation of PDK4 m6A by dm6ACRISPR decreases PDK4 expression and glycolysis. m6A-seq, YTHDF1/eEF-2/IGF2BP3 binding assays, dm6ACRISPR targeted demethylation, translation elongation assay, mRNA stability assay, glycolysis measurement, TBP ChIP at METTL3 promoter Nature communications High 32444598
2020 PDK4 drives vascular smooth muscle cell calcification by impairing autophagic flux via two mechanisms: (1) disrupting the integrity of mitochondria-associated endoplasmic reticulum membranes and impairing mitochondrial respiratory capacity, leading to decreased lysosomal V-ATPase and LDHB interaction; (2) inhibiting nuclear translocation of transcription factor EB (TFEB) to suppress lysosomal function. PDK4 also shifts VSMC metabolism toward a Warburg effect. PDK4 knockdown/overexpression in VSMCs, mitochondria-ER membrane integrity assay, V-ATPase/LDHB interaction analysis, TFEB nuclear translocation imaging, autophagic flux assay, calcium content measurement Cell death & disease Medium 33203874
2020 LKB1 represses ATOH1 expression in intestinal stem cells via PDK4. LKB1 loss increases PDK4 expression and alters metabolic profile; PDK4 knockdown or DCA inhibition reduces the upregulation of ATOH1 mRNA after LKB1 knockdown and partially restores oxygen consumption rate, placing PDK4 downstream of LKB1 in intestinal stem cell fate determination. LKB1 conditional KO mice, PDK4 siRNA knockdown, DCA treatment, ATOH1 mRNA measurement, Seahorse metabolic analysis, intestinal organoid assays, RNA-seq Gastroenterology Medium 31930988
2020 PDK4 deficiency in liver promotes regeneration after partial hepatectomy by enhancing insulin/Akt signaling and activating an AMPK/FOXO1/CD36 axis: PDK4 loss reduces intracellular AMP levels, activates AMPK, which phosphorylates and activates FOXO1 to suppress CD36 expression; conversely, PDK4 overexpression suppresses AMPK and allows CD36-mediated lipid uptake. PDK4-regulated AMPK activation directly depends on intracellular AMP. PDK4 KO mice with partial hepatectomy, in vitro AMP manipulation, AMPK/FOXO1/CD36 pathway measurement, CD36 overexpression, insulin signaling (IRS1/IRS2/Akt phosphorylation), liver/body weight ratio, hepatic DNA replication Hepatology communications Medium 32258946
2021 PDK4 inhibits ferroptosis in pancreatic ductal carcinoma cells by blocking pyruvate dehydrogenase (PDH)-dependent pyruvate oxidation, thereby reducing fatty acid synthesis that would otherwise fuel lipid peroxidation-dependent ferroptotic death. Glucose uptake via SLC2A1 promotes glycolysis and pyruvate oxidation to facilitate ferroptosis, while PDK4 acts as the top resistance gene against this pathway. siRNA library screen targeting metabolic enzymes, PDK4 siRNA knockdown, PDH activity assay, fatty acid synthesis measurement, lipid peroxidation assay, SLC2A1 manipulation, high-fat diet mouse model Cell reports High 33626342
2017 Progesterone induces PDK4 expression in cardiomyocytes during late pregnancy, leading to PDH inhibition (increased PDH phosphorylation) and reduced pyruvate flux into the TCA cycle, causing cardiac metabolic remodeling toward increased fatty acid oxidation and reduced glucose/lactate oxidation. Blocking PDK4 reverses these metabolic changes. 13C glucose/lactate/fatty acid tracing in isolated hearts, progesterone treatment of cardiomyocytes, PDK4 blockade, PDH phosphorylation measurement, late-pregnancy mouse model Circulation research High 28928113
2016 Arsenic silences hepatic PDK4 expression through activation of histone methyltransferase G9a, which increases H3K9 di- and tri-methylation (H3K9me2/3) at the PDK4 promoter. G9a siRNA knockdown induces PDK4 expression, and arsenic exposure antagonizes G9a inhibitor-mediated PDK4 induction. G9a inhibitor BRD4770, Suv39H inhibitor Chaetocin, arsenic treatment, G9a siRNA knockdown, ChIP for H3K9me2/3 at PDK4 promoter, PDK4 expression measurement in HCC cells and mouse liver Toxicology and applied pharmacology Medium 27217333
2022 PDK4 promotes mitochondrial fission through a non-canonical mechanism independent of PDC phosphorylation. A phosphoproteomic screen identified Septin 2 (SEPT2) as a PDK4 substrate; PDK4 phosphorylates SEPT2, which then acts as a receptor for DRP1 at the outer mitochondrial membrane to drive mitochondrial fragmentation. Inhibition of the PDK4-SEPT2 axis restores mitochondrial dynamics and cellular respiration in mitofusin 2-deficient cells. Phosphoproteomic screen for PDK4 substrates, non-phosphorylatable and phosphomimetic SEPT2 mutations, DRP1 localization to outer mitochondrial membrane, mitochondrial morphology imaging, mitofusin 2-deficient cell rescue, cellular respiration measurement, PDK4 KO cells with ETC toxins Proceedings of the National Academy of Sciences of the United States of America High 35969774
2023 Senescent cells upregulate PDK4, which drives aerobic glycolysis and enhanced lactate production while maintaining mitochondrial respiration. PDK4-dependent lactate promotes ROS production via NOX1, driving the senescence-associated secretory phenotype (SASP). PDK4 suppression reduces DNA damage severity and restrains SASP. PDK4 expression analysis in senescent cell lines, PDK4 inhibition/knockdown, lactate/ROS measurement, NOX1 pathway analysis, SASP factor measurement, in vivo PDK4 inhibition in tumor and aging models Nature metabolism High 37903887
2022 PDK4 overexpression promotes PDH phosphorylation, inhibits PDH activity, and changes cell metabolism after subarachnoid hemorrhage (SAH). PDK4 activity reduces ROS production and inhibits the ASK1/P38 apoptosis pathway in neurons, providing neuroprotection. PDK4 knockdown promotes ROS production, activates ASK1/P38, and induces neuronal apoptosis. siRNA PDK4 knockdown, lentiviral PDK4 overexpression, DCA PDK4 inhibition, PDH phosphorylation and activity measurement, ROS measurement, ASK1/P38 activation, neuronal apoptosis quantification, SAH rat model Antioxidants & redox signaling Medium 34498942
2024 PDK4 phosphorylates HDAC8 at Ser-39, activating HDAC8, which then deacetylates and suppresses CD20 protein expression, contributing to rituximab resistance in DLBCL. PDK4 protein localizes to both nucleus and cytoplasm in resistant cells. shRNA knockdown with RNA sequencing, immunofluorescence localization, Western blot, PDK4 phosphorylation of HDAC8 Ser-39 identified, CD20 deacetylation measurement, resistant DLBCL cell line and mouse model Molecular cancer Medium 39004737
2024 AMPK phosphorylation stimulates PDK4 expression, and SIRT1 physically interacts with PDK4 to promote glycolysis and facilitate endometrial stromal cell decidualization. Testosterone excess inhibits the AMPK/SIRT1/PDK4 pathway via androgen receptor activation, impairs PDK4 expression, and disrupts decidualization. Co-immunoprecipitation (SIRT1-PDK4 interaction), RNA-seq, PDK4 knockdown in vivo and in vitro, AMPK inhibitor/activator experiments, AR inhibition rescue, glycolysis measurement, decidualization markers (IGFBP1, PRL) Cellular and molecular life sciences Medium 39080028
2013 HIV-1 Vpr physically interacts with the ligand-binding domain of PPARbeta/delta in vitro and in vivo, and through this interaction enhances PPARbeta/delta-mediated transcription of PDK4 (1.9-fold increase in PDK4 protein), increasing inhibitory phosphorylation of PDH E1alpha and reducing PDC activity by 47%. PPARbeta/delta knockdown, Vpr-PPARbeta/delta in vitro and in vivo binding assay, PDK4 protein and mRNA measurement, PDH E1alpha phosphorylation, PDC activity assay, oxygen consumption measurement Molecular endocrinology (Baltimore, Md.) Medium 23842279
2020 WTAP mediates m6A modification of PDK4 mRNA; WTAP binds to m6A binding sites in PDK4 mRNA (confirmed by RNA pull-down assay). WTAP depletion increases PDK4 expression and suppresses colorectal cancer cell malignancy, while PDK4 silencing promotes cancer cell growth. MeRIP-qPCR for m6A quantification, RNA pull-down confirming WTAP-PDK4 mRNA interaction, shRNA knockdown of WTAP and PDK4, xenograft tumor models Current medicinal chemistry Medium 36154586
2006 Insulin's ability to suppress PDK4 mRNA expression in skeletal muscle is impaired in acute insulin-resistant states (induced by Intralipid or lactate infusion), concomitant with impaired insulin-stimulated phosphorylation of Akt and FOXO1, establishing that insulin suppresses PDK4 through the Akt-FOXO1 signaling axis. Euglycemic hyperinsulinemic clamp in insulin-resistant rats, Intralipid/lactate infusion, quantitative RT-PCR for PDK4, Akt and FOXO1 phosphorylation measurement Diabetes Medium 16873695

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 N6-methyladenosine regulates glycolysis of cancer cells through PDK4. Nature communications 264 32444598
2021 PDK4 dictates metabolic resistance to ferroptosis by suppressing pyruvate oxidation and fatty acid synthesis. Cell reports 220 33626342
1996 Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human. The Journal of biological chemistry 158 8798399
2011 Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation. Genes & development 153 21852536
2000 Targeted upregulation of pyruvate dehydrogenase kinase (PDK)-4 in slow-twitch skeletal muscle underlies the stable modification of the regulatory characteristics of PDK induced by high-fat feeding. Diabetes 149 10905486
2013 ANG II causes insulin resistance and induces cardiac metabolic switch and inefficiency: a critical role of PDK4. American journal of physiology. Heart and circulatory physiology 142 23396452
2023 PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy. Nature metabolism 141 37903887
2012 FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: therapeutic benefits of dichloroacetate. Journal of molecular medicine (Berlin, Germany) 130 23247844
2002 Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal. Physiological genomics 126 11842126
2019 Upregulated PDK4 expression is a sensitive marker of increased fatty acid oxidation. Mitochondrion 108 31351920
2008 CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress. The Journal of biological chemistry 104 18308721
2006 Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states. Diabetes 94 16873695
2018 The Role of Pyruvate Dehydrogenase Kinase-4 (PDK4) in Bladder Cancer and Chemoresistance. Molecular cancer therapeutics 93 29907593
2008 Regulation of the PDK4 isozyme by the Rb-E2F1 complex. The Journal of biological chemistry 93 18667418
2017 Oncogenic role of PDK4 in human colon cancer cells. British journal of cancer 92 28208156
2020 PDK4 promotes vascular calcification by interfering with autophagic activity and metabolic reprogramming. Cell death & disease 90 33203874
2012 A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher. Human genetics 86 22447147
2018 Restoring mitochondrial biogenesis with metformin attenuates β-GP-induced phenotypic transformation of VSMCs into an osteogenic phenotype via inhibition of PDK4/oxidative stress-mediated apoptosis. Molecular and cellular endocrinology 83 30170182
2018 Adropin regulates pyruvate dehydrogenase in cardiac cells via a novel GPCR-MAPK-PDK4 signaling pathway. Redox biology 76 29909017
2014 PDK4 protein promotes tumorigenesis through activation of cAMP-response element-binding protein (CREB)-Ras homolog enriched in brain (RHEB)-mTORC1 signaling cascade. The Journal of biological chemistry 75 25164809
2018 Advanced glycation end products accelerate calcification in VSMCs through HIF-1α/PDK4 activation and suppress glucose metabolism. Scientific reports 74 30213959
2018 Loss of PDK4 switches the hepatic NF-κB/TNF pathway from pro-survival to pro-apoptosis. Hepatology (Baltimore, Md.) 72 29603325
2019 PDK4 drives metabolic alterations and muscle atrophy in cancer cachexia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 68 30894018
2016 The microRNA-182-PDK4 axis regulates lung tumorigenesis by modulating pyruvate dehydrogenase and lipogenesis. Oncogene 68 27641336
2014 Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery 59 24837562
2009 Regulation of pyruvate dehydrogenase kinase 4 (PDK4) by thyroid hormone: role of the peroxisome proliferator-activated receptor gamma coactivator (PGC-1 alpha). The Journal of biological chemistry 59 19948729
2018 Targeting PDK4 inhibits breast cancer metabolism. American journal of cancer research 55 30323966
2020 STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer. Molecular systems biology 50 32323921
2017 PDK4 Inhibits Cardiac Pyruvate Oxidation in Late Pregnancy. Circulation research 50 28928113
2003 Reduced PDK4 expression associates with increased insulin sensitivity in postobese patients. Obesity research 50 12582211
2020 Down-regulation of lncRNA CASC9 aggravates sepsis-induced acute lung injury by regulating miR-195-5p/PDK4 axis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 49 32221619
2018 PDK4 Deficiency Suppresses Hepatic Glucagon Signaling by Decreasing cAMP Levels. Diabetes 48 30065033
2020 Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastasis and metabolic switch via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling in ovarian cancer. British journal of cancer 46 32390009
2017 Loss of the novel mitochondrial protein FAM210B promotes metastasis via PDK4-dependent metabolic reprogramming. Cell death & disease 46 28594398
2023 PDK4 rescues high-glucose-induced senescent fibroblasts and promotes diabetic wound healing through enhancing glycolysis and regulating YAP and JNK pathway. Cell death discovery 45 38001078
2020 Synovial fibroblast-derived exosomal microRNA-106b suppresses chondrocyte proliferation and migration in rheumatoid arthritis via down-regulation of PDK4. Journal of molecular medicine (Berlin, Germany) 45 32152704
2019 lncRNA PCAT19 promotes the proliferation of laryngocarcinoma cells via modulation of the miR-182/PDK4 axis. Journal of cellular biochemistry 45 30868666
2022 Noncanonical PDK4 action alters mitochondrial dynamics to affect the cellular respiratory status. Proceedings of the National Academy of Sciences of the United States of America 44 35969774
2020 LKB1 Represses ATOH1 via PDK4 and Energy Metabolism and Regulates Intestinal Stem Cell Fate. Gastroenterology 44 31930988
2004 Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA. American journal of physiology. Endocrinology and metabolism 44 15026305
2018 The miR-15b-5p/PDK4 axis regulates osteosarcoma proliferation through modulation of the Warburg effect. Biochemical and biophysical research communications 43 30093112
2019 Melatonin Therapy Modulates Cerebral Metabolism and Enhances Remyelination by Increasing PDK4 in a Mouse Model of Multiple Sclerosis. Frontiers in pharmacology 42 30873027
2020 PDK4-Deficiency Reprograms Intrahepatic Glucose and Lipid Metabolism to Facilitate Liver Regeneration in Mice. Hepatology communications 41 32258946
2010 Epinephrine-mediated regulation of PDK4 mRNA in rat adipose tissue. American journal of physiology. Cell physiology 41 20739620
2022 PDK4 Decrease Neuronal Apoptosis via Inhibiting ROS-ASK1/P38 Pathway in Early Brain Injury After Subarachnoid Hemorrhage. Antioxidants & redox signaling 40 34498942
2018 Putrescine delays postovulatory aging of mouse oocytes by upregulating PDK4 expression and improving mitochondrial activity. Aging 40 30554191
2018 MicroRNA-23a promotes colorectal cancer cell survival by targeting PDK4. Experimental cell research 39 30342991
2020 Advanced glycation end products enhance macrophage polarization to the M1 phenotype via the HIF-1α/PDK4 pathway. Molecular and cellular endocrinology 38 32464167
2021 microRNA-15b-5p shuttled by mesenchymal stem cell-derived extracellular vesicles protects podocytes from diabetic nephropathy via downregulation of VEGF/PDK4 axis. Journal of bioenergetics and biomembranes 37 34806156
2020 miR-16-5p/PDK4-Mediated Metabolic Reprogramming Is Involved in Chemoresistance of Cervical Cancer. Molecular therapy oncolytics 35 32577500
2015 ZBTB2 increases PDK4 expression by transcriptional repression of RelA/p65. Nucleic acids research 34 25609694
2019 Long non-coding RNA LINC00243 promotes proliferation and glycolysis in non-small cell lung cancer cells by positively regulating PDK4 through sponging miR-507. Molecular and cellular biochemistry 33 31595421
2019 HIF-1α/PDK4/autophagy pathway protects against advanced glycation end-products induced vascular smooth muscle cell calcification. Biochemical and biophysical research communications 32 31376939
2015 Inflammation increases pyruvate dehydrogenase kinase 4 (PDK4) expression via the Jun N-Terminal Kinase (JNK) pathway in C2C12 cells. Biochemical and biophysical research communications 32 26740179
2008 Characterization of the porcine differentially expressed PDK4 gene and association with meat quality. Molecular biology reports 32 19051057
2017 Nε-carboxymethyl-lysine promotes calcium deposition in VSMCs via intracellular oxidative stress-induced PDK4 activation and alters glucose metabolism. Oncotarget 31 29348870
2022 PRKCA Promotes Mitophagy through the miR-15a-5p/PDK4 Axis to Relieve Sepsis-Induced Acute Lung Injury. Infection and immunity 30 36448837
2016 Combined speed endurance and endurance exercise amplify the exercise-induced PGC-1α and PDK4 mRNA response in trained human muscle. Physiological reports 30 27456910
2023 Glucocorticoid Receptors Drive Breast Cancer Cell Migration and Metabolic Reprogramming via PDK4. Endocrinology 29 37224504
2017 Curcumin mediated down-regulation of αV β3 integrin and up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) in Erlotinib resistant SW480 colon cancer cells. Phytotherapy research : PTR 29 29168312
2016 Farnesoid X receptor activation promotes cell proliferation via PDK4-controlled metabolic reprogramming. Scientific reports 29 26728993
2007 Calcium signalling in the regulation of PGC-1alpha, PDK4 and HKII mRNA expression. Biological chemistry 29 17516843
2011 The effect of continuous and interval exercise on PGC-1α and PDK4 mRNA in type I and type II fibres of human skeletal muscle. Acta physiologica (Oxford, England) 28 21883960
2022 SIRT6 inhibits hypoxia-induced pulmonary arterial smooth muscle cells proliferation via HIF-1α/PDK4 signaling. Life sciences 27 36396113
2019 Geniposide Improves Glucose Homeostasis via Regulating FoxO1/PDK4 in Skeletal Muscle. Journal of agricultural and food chemistry 27 30929433
2015 Altered regulation of PDK4 expression promotes antiestrogen resistance in human breast cancer cells. SpringerPlus 27 26576332
2016 Arsenic silences hepatic PDK4 expression through activation of histone H3K9 methylatransferase G9a. Toxicology and applied pharmacology 26 27217333
2011 Regulation of pyruvate dehydrogenase kinase 4 (PDK4) by CCAAT/enhancer-binding protein beta (C/EBPbeta). The Journal of biological chemistry 26 21586575
2024 Ginsenoside Rh2 shifts tumor metabolism from aerobic glycolysis to oxidative phosphorylation through regulating the HIF1-α/PDK4 axis in non-small cell lung cancer. Molecular medicine (Cambridge, Mass.) 25 38671369
2021 LncRNA CASC2 Alleviates Sepsis-induced Acute Lung Injury by Regulating the miR-152-3p/PDK4 Axis. Immunological investigations 24 34165388
2023 Cardiomyocyte Pdk4 response is associated with metabolic maladaptation in aging. Aging cell 23 36797808
2019 Enhancing cardiac glycolysis causes an increase in PDK4 content in response to short-term high-fat diet. The Journal of biological chemistry 23 31562244
2020 Loss of PDK4 expression promotes proliferation, tumorigenicity, motility and invasion of hepatocellular carcinoma cells. Journal of Cancer 22 32489458
2017 Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts. Scientific reports 22 28814762
2014 The antineoplastic effect of carnosine is accompanied by induction of PDK4 and can be mimicked by L-histidine. Amino acids 22 24398899
2010 Effect of phase delay lighting rotation schedule on daily expression of per2, bmal1, rev-erbα, pparα, and pdk4 genes in the heart and liver of Wistar rats. Molecular and cellular biochemistry 22 21076970
2021 MiR-122-5p suppresses neuropathic pain development by targeting PDK4. Neurochemical research 21 33566299
2025 Validation and the role of PDK4 relevant to ferroptosis in degenerative lumbar disc disease. Journal of orthopaedic surgery and research 20 39794775
2021 Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle. Communications biology 20 34737380
2016 CK2 inhibition induced PDK4-AMPK axis regulates metabolic adaptation and survival responses in glioma. Experimental cell research 20 27001465
2024 Decreased AMPK/SIRT1/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS. Cellular and molecular life sciences : CMLS 19 39080028
2023 TUG1 protects against ferroptosis of hepatic stellate cells by upregulating PDK4-mediated glycolysis. Chemico-biological interactions 19 37582412
2021 Increased Expression of PDK4 Was Displayed in Gastric Cancer and Exhibited an Association With Glucose Metabolism. Frontiers in genetics 19 34220962
2021 MicroRNA -148 alleviates cardiac dysfunction, immune disorders and myocardial apoptosis in myocardial ischemia-reperfusion (MI/R) injury by targeting pyruvate dehydrogenase kinase (PDK4). Bioengineered 19 34517782
2020 PDK4 promotes tumorigenesis and cisplatin resistance in lung adenocarcinoma via transcriptional regulation of EPAS1. Cancer chemotherapy and pharmacology 19 33221963
2018 Diurnal Variation in PDK4 Expression Is Associated With Plasma Free Fatty Acid Availability in People. The Journal of clinical endocrinology and metabolism 18 29294006
2024 Unveiling the PDK4-centered rituximab-resistant mechanism in DLBCL: the potential of the "Smart" exosome nanoparticle therapy. Molecular cancer 17 39004737
2021 LINC00662 modulates cervical cancer cell proliferation, invasion, and apoptosis via sponging miR-103a-3p and upregulating PDK4. Molecular carcinogenesis 17 33819358
2021 circCCDC66 promotes thyroid cancer cell proliferation, migratory and invasive abilities and glycolysis through the miR-211-5p/PDK4 axis. Oncology letters 17 33841577
2020 Assessment of PDK4 and TTN gene variants in 48 Doberman Pinschers with dilated cardiomyopathy. Journal of the American Veterinary Medical Association 17 33135971
2016 Capric Acid Up-Regulates UCP3 Expression without PDK4 Induction in Mouse C2C12 Myotubes. Journal of nutritional science and vitaminology 17 27117849
2015 Pyruvate dehydrogenase kinase 4 (PDK4) could be involved in a regulatory role in apoptosis and a link between apoptosis and insulin resistance. Experimental and molecular pathology 17 25794976
2020 microRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4. Cancer gene therapy 16 33257740
2024 PDK4 inhibits osteoarthritis progression by activating the PPAR pathway. Journal of orthopaedic surgery and research 15 38308345
2022 LncRNA HCG11 promotes 5-FU resistance of colon cancer cells through reprogramming glucose metabolism by targeting the miR-144-3p-PDK4 axis. Cancer biomarkers : section A of Disease markers 15 34542064
2021 lncRNA GAS5 suppresses rheumatoid arthritis by inhibiting miR-361-5p and increasing PDK4. Biochemical and biophysical research communications 15 34715498
2019 High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases. British journal of cancer 15 30808993
2024 Dichloroacetate Prevents Sepsis Associated Encephalopathy by Inhibiting Microglia Pyroptosis through PDK4/NLRP3. Inflammation 14 39177920
2023 WTAP Mediated the N6-methyladenosine Modification of PDK4 to Regulate the Malignant Behaviors of Colorectal Cancer Cells In Vitro and In Vivo. Current medicinal chemistry 14 36154586
2013 HIV-1 Vpr enhances PPARβ/δ-mediated transcription, increases PDK4 expression, and reduces PDC activity. Molecular endocrinology (Baltimore, Md.) 14 23842279

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