Affinage

PDP1

[Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial · UniProt Q9P0J1

Length
537 aa
Mass
61.1 kDa
Annotated
2026-04-29
100 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Mammalian PDP1 (pyruvate dehydrogenase phosphatase catalytic subunit 1) is a mitochondrial Mg²⁺/Ca²⁺-dependent serine phosphatase that dephosphorylates the E1α subunit (PDHA1) of the pyruvate dehydrogenase complex (PDC), thereby activating PDC and controlling carbon flux from glycolysis into the TCA cycle; loss-of-function mutations in PDP1 cause PDC deficiency and congenital lactic acidosis (PMID:19184109, PMID:31392110). PDP1 catalytic activity is regulated by hierarchical post-translational modifications: ACAT1-mediated acetylation of K202 dissociates PDP1 from PDHA1 and inhibits its phosphatase activity, while SIRT3 deacetylation of K202 restores it, with Y381 phosphorylation toggling recruitment between ACAT1 and SIRT3; additionally, Rheb physically associates with PDP1 to enhance its activity and PDH-E1α binding in neurons (PMID:24486017, PMID:33725483). Beyond its canonical phosphatase role, PDP1 sustains acetyl-CoA production that supports histone H3 acetylation at HIF-1 target gene promoters under hypoxia, and a non-canonical scaffold function has been described in which PDP1 bridges BRAF and MEK1 to activate MAPK signaling in KRAS-mutant colorectal cancer (PMID:36453802, PMID:38849010).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2009 High

    Whether PDP1 is essential for PDC activation in humans was answered by identification of a homozygous null mutation (p.E93X) that abolished PDP1 protein and PDC activity in patient fibroblasts; recombinant PDP1 or PDP2 restored activity, establishing PDP1 as a non-redundant PDC activator and PDP2 as a compensatory isoform.

    Evidence Patient fibroblast biochemistry, immunoblotting, recombinant protein complementation

    PMID:19184109

    Open questions at the time
    • Tissue-specific contributions of PDP1 vs PDP2 not defined
    • Structural basis of PDP1–E1α interaction unknown
  2. 2014 High

    How PDP1 activity is tuned post-translationally was resolved: ACAT1 acetylates PDP1-K202 to dissociate PDHA1 and inhibit phosphatase activity, while SIRT3 deacetylates K202 to restore it; Y381 phosphorylation serves as a hierarchical switch that recruits ACAT1 and displaces SIRT3, linking mitochondrial signaling to PDC regulation.

    Evidence Mass spectrometry identification of modification sites, mutagenesis, Co-IP of ACAT1/SIRT3, tumor xenograft rescue

    PMID:24486017

    Open questions at the time
    • Kinase responsible for Y381 phosphorylation not identified
    • Whether this regulatory axis operates in non-cancer tissues is untested
  3. 2019 Medium

    A second human PDP1-null patient (biallelic c.575dupT) confirmed PDP1 deficiency as a cause of congenital lactic acidosis and unexpectedly revealed reduced BCKDH activity, raising the possibility that PDP1 regulates additional mitochondrial dehydrogenase complexes.

    Evidence Genetic sequencing, immunoblotting, PDC and BCKDH activity assays in patient fibroblasts

    PMID:31392110

    Open questions at the time
    • Direct dephosphorylation of BCKDH by PDP1 not demonstrated biochemically
    • Only a single patient; BCKDH link could be secondary
  4. 2021 High

    How upstream signaling activates PDP1 in neurons was established: Rheb is trafficked to the mitochondrial matrix via Tom20, where it physically binds PDP1 to enhance its phosphatase activity and association with PDH-E1α, coupling neuronal activity to PDH-dependent ATP production.

    Evidence Reciprocal Co-IP (Rheb–PDP1), cell-type-specific genetic models, PDH phosphorylation and metabolic assays, subcellular fractionation

    PMID:33725483

    Open questions at the time
    • Whether Rheb–PDP1 interaction is direct or mediated by an adaptor is not resolved at the structural level
    • Relevance of this axis outside the nervous system untested
  5. 2021 Medium

    PDP1 was placed in a mitochondrial Ca²⁺–PDH–nuclear histone acetylation axis: complex I deficiency elevates mitochondrial Ca²⁺, which paradoxically decreases PDP1 activity, reducing nuclear PDH-dependent histone acetylation and promoting DNA damage repair and radioresistance in colorectal cancer.

    Evidence Complex I knockdown/KO, Ca²⁺ manipulation, PDH activity assays, histone acetylation analysis, in vivo tumor models

    PMID:34489398

    Open questions at the time
    • Direct biochemical mechanism by which elevated Ca²⁺ inhibits rather than activates PDP1 not reconstituted
    • Effect observed only in cancer cell lines
  6. 2022 High

    PDP1's metabolic output was linked to chromatin regulation: PDP1 sustains acetyl-CoA production that fuels histone H3 acetylation at HIF-1 target gene promoters under hypoxia; PDP1 depletion reduces HIF-1 transcriptional activity without affecting HIF-1α protein levels, and acetate or HDAC inhibitor rescue confirms PDP1 acts upstream of chromatin acetylation.

    Evidence siRNA knockdown, ChIP, luciferase reporter, acetate/HDAC inhibitor rescue, Western blotting

    PMID:36453802

    Open questions at the time
    • Whether PDP1's effect on histone acetylation is specific to HIF targets or genome-wide is not determined
    • In vivo validation in animal models not performed
  7. 2024 Medium

    A non-canonical, phosphatase-independent function was proposed: PDP1 scaffolds BRAF–MEK1 interaction to activate MAPK signaling in KRAS-mutant colorectal cancer, with KLF5 driving PDP1 transcription; combined PDP1 and MAPK inhibitor targeting synergistically suppresses tumor growth.

    Evidence Co-IP of PDP1–BRAF–MEK1 complex, CRISPR knockout, overexpression in vitro/in vivo, luciferase reporter for KLF5–PDP1 promoter

    PMID:38849010

    Open questions at the time
    • Direct reconstitution of scaffold activity with purified components not shown
    • Whether phosphatase activity contributes to MAPK activation is unresolved
    • Independence from PDH regulation not formally excluded

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of PDP1–PDHA1 recognition, the identity of the Y381 kinase, whether PDP1 directly dephosphorylates BCKDH, and the relative physiological importance of PDP1's canonical phosphatase versus scaffold functions in vivo.
  • No crystal or cryo-EM structure of mammalian PDP1 or PDP1–substrate complex
  • Y381 kinase identity unknown
  • BCKDH dephosphorylation by PDP1 not reconstituted
  • Tissue-specific PDP1 vs PDP2 contributions poorly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005739 mitochondrion 5
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
ACAT1BRAFMEK1PDHA1RHEBSIRT3
Complex memberships
Pyruvate dehydrogenase complex (PDC)

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 PDP1 (pyruvate dehydrogenase phosphatase 1) is acetylated at K202 by the mitochondrial acetyltransferase ACAT1, which inhibits PDP1 activity by dissociating its substrate PDHA1; SIRT3 deacetylates PDP1 at K202 to restore activity. Additionally, Y381 phosphorylation of PDP1 dissociates SIRT3 and recruits ACAT1 to the PDH complex, providing hierarchical post-translational control. In vitro biochemical assays, mass spectrometry, Co-IP, knockdown/overexpression experiments, site-directed mutagenesis, tumor xenograft models Molecular cell High 24486017
2009 PDP1 null mutation (homozygous nonsense c.277G>T, p.E93X) causes complete absence of PDP1 protein in mitochondria and results in inability to activate the PDH complex (PDC); native PDC activity can be restored by addition of recombinant PDP1 or PDP2, demonstrating PDP2 as a compensatory isoform in PDP1 deficiency. Patient fibroblast biochemical assays, immunoblotting of mitochondrial fractions, recombinant protein complementation, dichloroacetate activation assay Human genetics High 19184109
2022 PDP1 stimulates HIF-1 transcriptional activity under hypoxia through acetyl-CoA-dependent histone H3 acetylation at HIF-1 target gene promoters; PDP1 depletion reduces histone acetylation and HIF-1 binding to hypoxia-response elements without affecting HIF-1α protein levels or nuclear localization. Supplementation with acetate or HDAC inhibitor trichostatin A rescues HIF activity upon PDP1 depletion, placing PDP1 upstream of chromatin acetylation in hypoxic HIF regulation. siRNA knockdown, chromatin immunoprecipitation (ChIP), luciferase reporter assays, acetate/HDAC inhibitor rescue experiments, Western blotting The FEBS journal High 36453802
2021 Rheb physically associates with PDP1 (PDH phosphatase), enhancing its activity and its association with the catalytic E1α subunit of PDH, thereby reducing PDH phosphorylation and increasing PDH activity for ATP production in response to neuronal activity. Rheb is trafficked to the mitochondrial matrix via interaction with Tom20. Co-IP (Rheb-PDP1 interaction), cell-type-specific gain/loss-of-function genetic models, PDH phosphorylation/activity assays, acetyl-CoA and ATP measurements, subcellular fractionation Developmental cell High 33725483
2021 Mitochondrial complex I deficiency leads to decreased PDP1 activity via elevated mitochondrial Ca2+ ([Ca2+]m), reducing PDH activity in both cytoplasm and nucleus ([Ca2+]m–PDP1–PDH axis), which decreases nuclear PDH and histone acetylation, thereby promoting DNA damage repair and radioresistance in colorectal cancer cells. Complex I knockdown/knockout, Ca2+ manipulation, PDH activity assays, histone acetylation analysis, in vivo tumor models, correlation with patient radiotherapy outcomes Cell death & disease Medium 34489398
2023 PDP1 acts as a scaffold protein that enhances the interaction between BRAF and MEK1, thereby activating MAPK signaling and promoting KRAS mutant colorectal cancer progression; KLF5 is identified as the transcriptional regulator driving PDP1 upregulation in KRAS mutant CRC. FLT3-ITD induces PDP1 expression through the RAS signaling axis in AML. Co-IP (PDP1-BRAF-MEK1 scaffold function), CRISPR screens, endogenous tagging, knockdown/overexpression, in vitro and in vivo tumor models, NMR metabolic profiling Cancer letters; Leukemia Medium 37935978 38849010
2010 PDP1/PPAPDC2 (an integral membrane lipid phosphatase) preferentially hydrolyzes polyisoprenoid diphosphates including farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) in vitro; in mammalian cells it localizes to the endoplasmic reticulum and nuclear envelope with its catalytic domain facing the cytoplasm; overexpression decreases protein isoprenylation and causes defects in cell growth and cytoskeletal organization via dysregulation of Rho GTPases. Tandem mass spectrometry phosphatase assays with recombinant protein, yeast growth/sterol auxotrophy assay, subcellular fractionation/localization, overexpression in mammalian cells with cytoskeletal readouts The Journal of biological chemistry High 20110354
2011 In C. elegans, PDP-1 (a phosphatase) negatively regulates the insulin/IGF-1 signaling (IIS) pathway by promoting DAF-16 nuclear localization and transcriptional activity; genetic epistasis places PDP-1 in the DAF-7/TGF-β pathway at the level of R-SMAD proteins DAF-14 and DAF-8, and PDP-1 modulates the expression of insulin genes that feed into IIS. C. elegans genetics, epistasis analysis (double mutants), DAF-16 nuclear localization imaging, longevity/fat storage/dauer assays, gene expression analysis PLoS genetics Medium 21533078
2012 The fission yeast Pdp1 PWWP domain binds both H4K20me3 (trimethylated H4K20) via an aromatic cage and double-stranded DNA via a positively charged area; the domain associates with Set9 methyltransferase to regulate its chromatin localization and H4K20 methyltransferase activity; PWWP domain mutations that disrupt nucleosome binding reduce H4K20 di- and tri-methylation in yeast cells. Solution NMR structure determination, EMSA, mutagenesis, in vivo H4K20 methylation assays in yeast The Biochemical journal High 22150589
2019 A novel biallelic frameshift mutation (c.575dupT) in the human PDP1 gene causes absence of PDP1 protein in fibroblasts, PDC deficiency, and congenital lactic acidosis; the patient also showed unexpectedly low branched-chain 2-ketoacid dehydrogenase (BCKDH) activity without BCKDH mutations, suggesting potential shared regulatory function of PDP1 on multiple dehydrogenase complexes. Genetic sequencing, immunoblotting, PDC activity assays in lymphocytes and fibroblasts, DCA activation assay JIMD reports Medium 31392110
2003 Drosophila PDP1 (PAR domain protein 1, isoform epsilon) directly activates dClock (Clk) transcription in a second feedback loop of the circadian clock; VRI represses dClock expression while PDP1 activates it, with VRI levels peaking 3–6 hours before PDP1 to create temporal separation; a Pdp1 null mutant stops the circadian clock, identifying Pdp1 as an essential clock gene. Drosophila genetics (null mutant analysis), molecular rhythm analysis, transcriptional reporter assays, epistasis with vri Cell High 12581523
2009 The Drosophila PDP1epsilon isoform-specific mutant is viable, arrhythmic, and shows diminished CLK and PER expression in central clock cells, reduced PDF expression in a subset of clock neurons, and altered CLK phosphorylation status; transgenic PDP1epsilon rescues behavioral rhythms, but CLK overexpression in the mutant rescues PER expression without restoring behavioral rhythms, indicating PDP1epsilon functions both within the core oscillator and in output pathways. Drosophila isoform-specific mutant generation, behavioral rhythm assays, immunostaining, luciferase reporter (per-luc) in peripheral clocks, transgenic rescue The Journal of neuroscience High 19726650
1997 Drosophila PDP1 is a PAR-domain bZIP transcription factor that binds DNA sequences within the Tropomyosin I (TmI) gene muscle activator element required for somatic muscle expression; PDP1 binding site mutations eliminate muscle activator function; PDP1 functions as part of a protein/DNA complex that interacts with MEF2 to regulate Drosophila muscle gene transcription. Biochemical DNA binding assays, transient transfection reporter assays, enhancer mutation analysis, in situ expression studies Development (Cambridge, England) High 9409684
2000 The Pdp1 gene encodes at least six PDP1 isoforms through multiple transcriptional start sites, differential splicing and promoter usage; a sixth isoform lacking the PAR and basic DNA-binding domains functions as a dominant-negative inhibitor of transcription; different isoforms are differentially expressed in distinct tissues during development. cDNA cloning, Northern blot, in situ hybridization, DNA binding assays, transient transfection reporter assays Developmental biology Medium 10926776
2010 In Drosophila, the circadian clock Pdp1epsilon isoform regulates xenobiotic detoxification by controlling expression of cytochrome P450 enzymes (Cyp6a2, Cyp6g1) and alpha-Esterase-7; Pdp1epsilon-deficient flies show increased pesticide mortality; Pdp1 regulates DHR96 (a homolog of constitutive androstane/pregnane X receptors) expression, placing Pdp1 in a pathway from positive clock elements to detoxification effector genes. Drosophila genetics (Pdp1epsilon mutant), pesticide mortality assays, qRT-PCR gene expression analysis, epistasis with cyc/per/tim Toxicological sciences Medium 20348229
2005 Drosophila Pdp1 null larvae (Pdp1p205 allele) show normal embryonic muscle, gut, and fat body patterning but are severely growth delayed and arrested at the larval stage, failing to pupariate; defects include abnormal mitosis and endoreplication that are not cell-autonomous and are sensitive to nutritional conditions, indicating PDP1 coordinates nutrition-dependent growth and DNA replication. Drosophila null mutant analysis (Pdp1p205), clonal analysis for cell autonomy, tissue histology, growth measurements, ecdysone response assays Developmental biology Medium 16313897
2024 PDP1 (pyruvate dehydrogenase phosphatase catalytic subunit 1) acts as a scaffold protein that enhances the interaction between BRAF and MEK1 to activate MAPK signaling in KRAS mutant colorectal cancer; KLF5 transcription factor drives PDP1 upregulation; combined targeting of PDP1 with MAPK inhibitors synergistically inhibits KRAS mutant CRC growth. Co-immunoprecipitation (BRAF-MEK1-PDP1 complex), CRISPR/KO, overexpression in vitro and in vivo, luciferase reporter (KLF5-PDP1 promoter), patient tissue analysis Cancer letters Medium 38849010

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock. Cell 423 12581523
2014 Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex. Molecular cell 253 24486017
1998 Regulation of skeletal muscle glycogen phosphorylase and PDH at varying exercise power outputs. The American journal of physiology 144 9688676
1999 PUFA and aging modulate cardiac mitochondrial membrane lipid composition and Ca2+ activation of PDH. The American journal of physiology 131 9887028
2001 Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet. American journal of physiology. Endocrinology and metabolism 128 11701428
2003 PDP: protein domain parser. Bioinformatics (Oxford, England) 117 12584135
2022 Smart PdH@MnO2 Yolk-Shell Nanostructures for Spatiotemporally Synchronous Targeted Hydrogen Delivery and Oxygen-Elevated Phototherapy of Melanoma. ACS nano 97 35315637
2020 Selective Transfer Semihydrogenation of Alkynes with H2 O (D2 O) as the H (D) Source over a Pd-P Cathode. Angewandte Chemie (International ed. in English) 81 32777146
2021 DCA Protects against Oxidation Injury Attributed to Cerebral Ischemia-Reperfusion by Regulating Glycolysis through PDK2-PDH-Nrf2 Axis. Oxidative medicine and cellular longevity 73 34712383
1990 Comparative epitope mapping of murine monoclonal and human autoantibodies to human PDH-E2, the major mitochondrial autoantigen of primary biliary cirrhosis. Journal of immunology (Baltimore, Md. : 1950) 69 1690773
2001 Muscle fiber type comparison of PDH kinase activity and isoform expression in fed and fasted rats. American journal of physiology. Regulatory, integrative and comparative physiology 68 11171643
2021 Melatonin inhibits lung cancer development by reversing the Warburg effect via stimulating the SIRT3/PDH axis. Journal of pineal research 67 34214200
2009 The roles of aldehyde dehydrogenases (ALDHs) in the PDH bypass of Arabidopsis. BMC biochemistry 67 19320993
1996 Dra-nupC-pdp operon of Bacillus subtilis: nucleotide sequence, induction by deoxyribonucleosides, and transcriptional regulation by the deoR-encoded DeoR repressor protein. Journal of bacteriology 65 8550462
2016 Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma. Oncotarget 64 27474170
2005 PDH kinase inhibitors: a novel therapy for Type II diabetes? Biochemical Society transactions 64 15787608
2015 The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation. Molecular cancer therapeutics 60 25995437
2011 PDP-1 links the TGF-β and IIS pathways to regulate longevity, development, and metabolism. PLoS genetics 59 21533078
2017 Improving acetyl-CoA biosynthesis in Saccharomyces cerevisiae via the overexpression of pantothenate kinase and PDH bypass. Biotechnology for biofuels 58 28239413
2018 Poldip2 is an oxygen-sensitive protein that controls PDH and αKGDH lipoylation and activation to support metabolic adaptation in hypoxia and cancer. Proceedings of the National Academy of Sciences of the United States of America 56 29434038
2004 Simulation of Drosophila circadian oscillations, mutations, and light responses by a model with VRI, PDP-1, and CLK. Biophysical journal 54 15111397
2018 Pyruvate Dehydrogenase PDH-E1β Controls Tumor Progression by Altering the Metabolic Status of Cancer Cells. Cancer research 52 29436427
1988 Localization of pigment-dispersing hormone (PDH) immunoreactivity in the central nervous system of Carcinus maenas and Orconectes limosus (Crustacea), with reference to FMRFamide immunoreactivity in O. limosus. Cell and tissue research 48 3416337
2006 Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity. American journal of medical genetics. Part A 47 16770810
2004 Pigment-dispersing hormone (PDH)-immunoreactive neurons form a direct coupling pathway between the bilaterally symmetric circadian pacemakers of the cockroach Leucophaea maderae. Cell and tissue research 47 15578273
2011 Beneficial effect of pyruvate therapy on Leigh syndrome due to a novel mutation in PDH E1α gene. Brain & development 46 21454027
2021 Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxylic acid (TCA) cycle in hypoxic KRAS mutant colon cancer. Theranostics 45 33664850
2021 Rheb mediates neuronal-activity-induced mitochondrial energetics through mTORC1-independent PDH activation. Developmental cell 44 33725483
2012 Solution structure of the Pdp1 PWWP domain reveals its unique binding sites for methylated H4K20 and DNA. The Biochemical journal 44 22150589
2009 An isoform-specific mutant reveals a role of PDP1 epsilon in the circadian oscillator. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 19726650
1997 Neurites of period-expressing PDH cells in the fly's optic lobe exhibit circadian oscillations in morphology. The European journal of neuroscience 42 9283834
1997 PDP1, a novel Drosophila PAR domain bZIP transcription factor expressed in developing mesoderm, endoderm and ectoderm, is a transcriptional regulator of somatic muscle genes. Development (Cambridge, England) 42 9409684
2019 Lactic acidosis caused by repressed lactate dehydrogenase subunit B expression down-regulates mitochondrial oxidative phosphorylation via the pyruvate dehydrogenase (PDH)-PDH kinase axis. The Journal of biological chemistry 39 30923124
2000 Pyruvate overrides inhibition of PDH during exercise after a low-carbohydrate diet. American journal of physiology. Endocrinology and metabolism 39 10913026
2000 The Drosophila PAR domain protein 1 (Pdp1) gene encodes multiple differentially expressed mRNAs and proteins through the use of multiple enhancers and promoters. Developmental biology 39 10926776
2021 Mitochondrial dysfunction induces radioresistance in colorectal cancer by activating [Ca2+]m-PDP1-PDH-histone acetylation retrograde signaling. Cell death & disease 38 34489398
1991 Differential distribution of beta-pigment-dispersing hormone (beta-PDH)-like immunoreactivity in the stomatogastric nervous system of five species of decapod crustaceans. Cell and tissue research 37 1913777
2010 Circadian clock regulates response to pesticides in Drosophila via conserved Pdp1 pathway. Toxicological sciences : an official journal of the Society of Toxicology 34 20348229
1999 Identification and characterization of a DeoR-specific operator sequence essential for induction of dra-nupC-pdp operon expression in Bacillus subtilis. Journal of bacteriology 34 10074062
2019 pdh modulate virulence through reducing stress tolerance and biofilm formation of Streptococcus suis serotype 2. Virulence 33 31232165
2017 Regulation of pyruvate dehydrogenase (PDH) in the hibernating ground squirrel, (Ictidomys tridecemlineatus). Journal of thermal biology 33 29037383
2016 Age-related impairments in skeletal muscle PDH phosphorylation and plasma lactate are indicative of metabolic inflexibility and the effects of exercise training. American journal of physiology. Endocrinology and metabolism 32 27221120
2007 Regulation of PDH in human arm and leg muscles at rest and during intense exercise. American journal of physiology. Endocrinology and metabolism 31 17957032
2008 Cloning and differential expression of two beta-pigment-dispersing hormone (beta-PDH) isoforms in the crab Cancer productus: evidence for authentic beta-PDH as a local neurotransmitter and beta-PDH II as a humoral factor. The Journal of comparative neurology 30 18311785
2014 Prolyl-hydroxylase PHD3 interacts with pyruvate dehydrogenase (PDH)-E1β and regulates the cellular PDH activity. Biochemical and biophysical research communications 29 25088999
1998 TNF binding protein prevents hyperlactatemia and inactivation of PDH complex in skeletal muscle during sepsis. The Journal of surgical research 29 9790813
1996 Fasting and decreased B cell sensitivity: important role for fatty acid-induced inhibition of PDH activity. The American journal of physiology 29 8764183
2010 Functional characterization of the atypical integral membrane lipid phosphatase PDP1/PPAPDC2 identifies a pathway for interconversion of isoprenols and isoprenoid phosphates in mammalian cells. The Journal of biological chemistry 28 20110354
2019 Structural and Functional Analyses of the Human PDH Complex Suggest a "Division-of-Labor" Mechanism by Local E1 and E3 Clusters. Structure (London, England : 1993) 27 31130485
2009 Low muscle glycogen and elevated plasma free fatty acid modify but do not prevent exercise-induced PDH activation in human skeletal muscle. Diabetes 27 19833896
1986 Phytohemagglutinin (PHA) activated human T-lymphocytes: concomitant appearance of insulin binding, degradation and insulin-mediated activation of pyruvate dehydrogenase (PDH). Biochemical and biophysical research communications 27 3511901
2003 Regulation of PDH activity and isoform expression: diet and exercise. Biochemical Society transactions 26 14641042
1990 Antibody binding and inhibition of pyruvate dehydrogenase (PDH) in sera from patients with primary biliary cirrhosis. Clinical and experimental immunology 26 2387091
2010 PGC-1alpha increases PDH content but does not change acute PDH regulation in mouse skeletal muscle. American journal of physiology. Regulatory, integrative and comparative physiology 25 20720174
1993 Characterization of PDH beta 1, the structural gene for the pyruvate dehydrogenase beta subunit from Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 25 8433986
2017 PGC-1α and fasting-induced PDH regulation in mouse skeletal muscle. Physiological reports 24 28400503
2017 Metschnikowia pulcherrima Influences the Expression of Genes Involved in PDH Bypass and Glyceropyruvic Fermentation in Saccharomyces cerevisiae. Frontiers in microbiology 24 28702001
2009 Pyruvate dehydrogenase phosphatase 1 (PDP1) null mutation produces a lethal infantile phenotype. Human genetics 24 19184109
1993 Structure and localization of mRNA encoding a pigment dispersing hormone (PDH) in the eyestalk of the crayfish Orconectes limosus. FEBS letters 24 8477858
1991 Fraction of hepatic cytosolic acetyl-CoA derived from glucose in vivo: relation to PDH phosphorylation state. The American journal of physiology 24 2058663
2019 PDH-mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 30939245
2012 Protein domain histochemistry (PDH): binding of the carbohydrate recognition domain (CRD) of recombinant human glycoreceptor CLEC10A (CD301) to formalin-fixed, paraffin-embedded breast cancer tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 23 23275449
2011 PDH activation during in vitro muscle contractions in PDH kinase 2 knockout mice: effect of PDH kinase 1 compensation. American journal of physiology. Regulatory, integrative and comparative physiology 22 21411764
2023 Enabling growth-decoupled Komagataella phaffii recombinant protein production based on the methanol-free PDH promoter. Frontiers in bioengineering and biotechnology 21 37034257
1992 Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the E1 alpha subunit. Human genetics 21 1551669
2024 Baicalin attenuates neuronal damage associated with SDH activation and PDK2-PDH axis dysfunction in early reperfusion. Phytomedicine : international journal of phytotherapy and phytopharmacology 20 38579645
2010 The pdh operon is expressed in a subpopulation of stationary-phase bacteria and is important for survival of sugar-starved Streptococcus mutans. Journal of bacteriology 20 20581205
2009 PDH E1β deficiency with novel mutations in two patients with Leigh syndrome. Journal of inherited metabolic disease 20 19924563
2005 Elevated n-3 fatty acids in a high-fat diet attenuate the increase in PDH kinase activity but not PDH activity in human skeletal muscle. Journal of applied physiology (Bethesda, Md. : 1985) 20 15591305
2002 Glucose-stimulated insulin secretion does not require activation of pyruvate dehydrogenase: impact of adenovirus-mediated overexpression of PDH kinase and PDH phosphate phosphatase in pancreatic islets. Biochemical and biophysical research communications 20 11866475
1991 Pyruvate dehydrogenase deficiency due to a 20-bp deletion in exon II of the pyruvate dehydrogenase (PDH) E1 alpha gene. American journal of human genetics 20 1907799
2014 Two beta-pigment-dispersing hormone (β-PDH) isoforms in the mud crab, Scylla paramamosain: implication for regulation of ovarian maturation and a photoperiod-related daily rhythmicity. Animal reproduction science 19 25262380
2012 Cafestol to Tricalysiolide B and Oxidized Analogues: Biosynthetic and Derivatization Studies Using Non-heme Iron Catalyst Fe(PDP). Synlett : accounts and rapid communications in synthetic organic chemistry 19 23585710
2000 Catabolite repression of dra-nupC-pdp operon expression in Bacillus subtilis. Microbiology (Reading, England) 19 11065368
2022 Abnormal lipid droplets accumulation induced cognitive deficits in obstructive sleep apnea syndrome mice via JNK/SREBP/ACC pathway but not through PDP1/PDC pathway. Molecular medicine (Cambridge, Mass.) 18 35030992
2022 Pyruvate dehydrogenase phosphatase 1 (PDP1) stimulates HIF activity by supporting histone acetylation under hypoxia. The FEBS journal 18 36453802
2010 An animal model of PDH deficiency using AAV8-siRNA vector-mediated knockdown of pyruvate dehydrogenase E1α. Molecular genetics and metabolism 18 20685142
2006 Modelling of circadian rhythms in Drosophila incorporating the interlocked PER/TIM and VRI/PDP1 feedback loops. Journal of theoretical biology 17 17157878
2023 PDP1 is a key metabolic gatekeeper and modulator of drug resistance in FLT3-ITD-positive acute myeloid leukemia. Leukemia 16 37935978
2011 Role of pyruvate dehydrogenase kinase 4 in regulating PDH activation during acute muscle contraction. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 16 22196220
2019 Metabolic reorganization in winter: Regulation of pyruvate dehydrogenase (PDH) during long-term freezing and anoxia. Cryobiology 15 30639451
2010 Precursor structure, distribution and possible functions of pigment-dispersing hormone (PDH) in the terrestrial isopod Armadillidium vulgare (Latreille). Journal of insect physiology 15 20637211
2023 PdP2 Nanoparticles on Reduced Graphene Oxide: A Catalyst for the Electrocatalytic Reduction of Nitrate to Ammonia. Inorganic chemistry 14 37074289
2022 MiR-18a-3p improves cartilage matrix remodeling and inhibits inflammation in osteoarthritis by suppressing PDP1. The journal of physiological sciences : JPS 14 35148687
2020 Porcine Digestible Peptides (PDP) in Weanling Diets Regulates the Expression of Genes Involved in Gut Barrier Function, Immune Response and Nutrient Transport in Nursery Pigs. Animals : an open access journal from MDPI 14 33321976
2005 The Drosophila Par domain protein I gene, Pdp1, is a regulator of larval growth, mitosis and endoreplication. Developmental biology 14 16313897
1997 Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis. Journal of gastroenterology and hepatology 14 9504898
1995 Association of cerebral dysgenesis and lactic acidemia with X-linked PDH E1 alpha subunit mutations in females. Pediatric neurology 14 8771169
2023 Loss of muscle PDH induces lactic acidosis and adaptive anaplerotic compensation via pyruvate-alanine cycling and glutaminolysis. The Journal of biological chemistry 13 37865313
1999 Characterization of cryptic plasmids pDP1 and pSMB1 of Streptococcus pneumoniae. Plasmid 13 9887308
1996 Evolution of mammalian X-linked and autosomal Pgk and Pdh E1 alpha subunit genes. Molecular biology and evolution 13 8752009
1988 Retention of soman in rats, guinea-pigs and marmosets: species-dependent effects of the soman simulator, pinacolyl dimethylphosphinate (PDP). The Journal of pharmacy and pharmacology 13 2896771
2021 Application Route and Immune Status of the Host Determine Safety and Oncolytic Activity of Oncolytic Coxsackievirus B3 Variant PD-H. Viruses 12 34696348
2019 A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1) causing pyruvate dehydrogenase complex deficiency. JIMD reports 12 31392110
2017 Induction of the PDH bypass and upregulation of the ALDH7B4 in plants treated with herbicides inhibiting amino acid biosynthesis. Plant science : an international journal of experimental plant biology 12 28969796
2001 A case of PDH-E1 alpha mosaicism in a male patient with severe metabolic lactic acidosis. Journal of inherited metabolic disease 12 11757583
2000 Sequential deletion of C-terminal amino acids of the E(1)alpha component of the pyruvate dehydrogenase (PDH) complex leads to reduced steady-state levels of functional E(1)alpha(2)beta(2) tetramers: implications for patients with PDH deficiency. Human molecular genetics 12 10767328
1991 Primary structure and relative potency of an analog of beta-PDH (pigment-dispersing hormone) from the crayfish Procambarus clarkii. Pigment cell research 12 1823925
2024 PDP1 promotes KRAS mutant colorectal cancer progression by serving as a scaffold for BRAF and MEK1. Cancer letters 11 38849010
2021 Evaluation of immune effect of Streptococcus suis biofilm-associated protein PDH. Veterinary microbiology 11 34749282