Affinage

ME2

NAD-dependent malic enzyme, mitochondrial · UniProt P23368

Round 2 corrected
Length
584 aa
Mass
65.4 kDa
Annotated
2026-04-28
80 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ME2 is a mitochondrial NAD(P)⁺-dependent malic enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate, generating NADH and NADPH critical for mitochondrial respiration, biosynthetic reactions, and redox homeostasis (PMID:1993674, PMID:10700286). The enzyme functions as a tetramer whose activity is allosterically activated by fumarate at the dimer interface and inhibited by ATP at the active site, and is further modulated by post-translational modifications—desuccinylation at K346 by SIRT5, acetylation at K156 by ACAT1, and methylation at R67 by PRMT1—each of which potentiates catalytic activity to support tumor metabolism (PMID:12121650, PMID:38007551, PMID:39951294, PMID:39528487). ME2 loss diminishes NADPH production, elevates ROS, and activates AMPK, which suppresses SREBP1/BCAT2 signaling and triggers p53-dependent senescence, linking ME2 to metabolic adaptation and cell fate decisions in cancer (PMID:23334421, PMID:28099419). A homozygous loss-of-function ME2 variant (p.Phe460fs*22) causes a Mendelian disorder characterized by neurodevelopmental impairment, dilated cardiomyopathy, and lactic acidemia (PMID:39401966).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1991 High

    Cloning and heterologous expression of human ME2 established its identity as the mitochondrial NAD(P)⁺-dependent malic enzyme catalyzing oxidative decarboxylation of malate to pyruvate, resolving the molecular basis of an activity long known biochemically.

    Evidence cDNA cloning, E. coli expression, kinetic and allosteric characterization

    PMID:1993674

    Open questions at the time
    • No structural information on subunit assembly or allosteric sites
    • Regulation of expression unknown
  2. 2002 High

    High-resolution crystal structures of ME2 with substrates, cofactors, and allosteric effectors revealed that ATP inhibits at the active site, while fumarate activates through a dimer-interface allosteric site, providing the structural basis for cooperative regulation.

    Evidence X-ray crystallography (2.2 Å) of multiple quaternary complexes, site-directed mutagenesis, enzyme kinetics

    PMID:10700286 PMID:12121650

    Open questions at the time
    • Physiological relevance of allosteric regulation in vivo not tested
    • No structural data on post-translational modification sites
  3. 2013 High

    The discovery that p53 transcriptionally represses ME2, and that ME2 loss reciprocally activates p53 through AMPK, established a metabolic–tumor-suppressor feedback loop wherein ME2 depletion drives senescence rather than apoptosis.

    Evidence Genetic knockdown/overexpression with epistasis analysis in human and mouse cells, senescence assays, metabolic measurements

    PMID:23334421

    Open questions at the time
    • Specific AMPK substrates mediating p53 activation not fully identified
    • Whether ME2-driven senescence occurs in non-cancerous tissues in vivo unclear
  4. 2014 High

    ME2 depletion in NSCLC cells demonstrated that ME2 sustains tumor proliferation by maintaining NADPH/ROS balance and PI3K/AKT signaling, and that its loss sensitizes tumors to cisplatin, broadening ME2's role beyond metabolism to oncogenic signaling.

    Evidence shRNA knockdown, stable isotope metabolic tracing, xenograft tumor models, kinase signaling analysis

    PMID:24957098

    Open questions at the time
    • Mechanism linking ME2 to PDK1/PTEN expression not fully resolved
    • No demonstration with genetic knockout
  5. 2015 High

    Identification of embonic acid as an allosteric ME2 inhibitor binding near the fumarate site provided pharmacological validation that ME2 inhibition induces senescence, even in p53-null cells, indicating both p53-dependent and -independent effector pathways.

    Evidence In vitro inhibition kinetics, site-directed mutagenesis of fumarate site, shRNA knockdown, cellular senescence assays in H1299 (p53-null) cells

    PMID:26008970

    Open questions at the time
    • In vivo pharmacokinetics and selectivity of embonic acid not characterized
    • p53-independent senescence pathway mediators unidentified
  6. 2017 High

    Collateral lethality of ME2 co-deletion with SMAD4 in pancreatic cancer revealed that combined loss of mitochondrial malic enzymes (ME2+ME3) collapses NADPH, activates AMPK, suppresses SREBP1-directed BCAT2 transcription, and depletes branched-chain amino acid-derived glutamate needed for nucleotide synthesis.

    Evidence CRISPR/shRNA depletion, integrated metabolomics, AMPK–SREBP1–BCAT2 epistasis analysis in pancreatic cancer models

    PMID:28099419

    Open questions at the time
    • Relative contributions of ME2 vs. ME3 to NADPH pool not individually quantified
    • Clinical feasibility of exploiting collateral lethality untested
  7. 2023 High

    Three post-translational modifications activating ME2 were identified: SIRT5-mediated desuccinylation at K346 under glutamine deprivation, ACAT1-mediated acetylation at K156 under glucose deprivation, and PRMT1-mediated methylation at R67, each enhancing ME2 catalytic activity to support tumor-adaptive metabolism.

    Evidence Co-immunoprecipitation, site-directed mutagenesis of K346/K156/R67, succinylation/acetylation/methylation assays, enzymatic activity assays, xenograft models

    PMID:38007551 PMID:39528487 PMID:39951294

    Open questions at the time
    • Crosstalk or hierarchy among the three modifications not examined
    • Structural basis for how each modification increases catalytic activity unknown
    • Whether these modifications co-occur in the same tumor type is unclear
  8. 2024 High

    AKT1 phosphorylation of a cytoplasmic ME2 full-length isoform at S9 blocks mitochondrial import and repurposes ME2 as a scaffold for glycolytic enzyme assembly (PFKL, GAPDH, PKM2, LDHA), uncovering a non-enzymatic moonlighting function that promotes a glycolytic metabolic switch.

    Evidence In vitro phosphorylation, S9 mutagenesis, subcellular fractionation, co-immunoprecipitation of glycolytic complex, metabolic flux, xenograft in vivo

    PMID:38263319

    Open questions at the time
    • Proportion of ME2 retained in cytoplasm under physiological conditions unknown
    • Whether scaffold function requires ME2 enzymatic activity is untested
    • Independent replication of this moonlighting role pending
  9. 2024 Medium

    A homozygous frameshift ME2 variant in a human patient established ME2 deficiency as a cause of neurodevelopmental disorder with dilated cardiomyopathy and lactic acidemia, and yeast complementation confirmed its essential mitochondrial function.

    Evidence Whole exome sequencing, in vitro protein stability assay, yeast ortholog deletion/complementation

    PMID:39401966

    Open questions at the time
    • Only a single family reported; additional kindreds needed
    • Patient-derived cell metabolomics not performed
    • Tissue-specific consequences of ME2 loss in mammals not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how the multiple post-translational activating modifications of ME2 are coordinated, what determines whether ME2 loss triggers senescence versus apoptosis versus ferroptosis across cell types, and whether the cytoplasmic scaffolding function operates in non-tumor physiology.
  • No integrated model of PTM crosstalk on ME2
  • Tissue-specific phenotypic outcomes of ME2 loss poorly defined
  • Structural basis of cytoplasmic scaffold assembly unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 7 GO:0016829 lyase activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005739 mitochondrion 5 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 10 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 3
Partners
ACAT1AKT1GAPDHLDHAPFKLPKM2PRMT1SIRT5

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Human mitochondrial NAD(P)+-dependent malic enzyme (ME2) was cloned from cDNA, revealing a 584-amino acid precursor protein (65.4 kDa). Expression of the processed protein in E. coli yielded an enzyme with the same kinetic and allosteric properties as malic enzyme purified from human cells, confirming its role in oxidative decarboxylation of malate to pyruvate with NAD+ as cofactor. cDNA cloning, heterologous expression in E. coli, enzymatic kinetic assays The Journal of biological chemistry High 1993674
2000 Crystal structure of human mitochondrial NAD(P)+-dependent ME2 in a quaternary complex with NAD+, Mn2+, and oxalate (2.2 Å) revealed the enzyme in a closed form. The divalent cation is coordinated octahedrally by Glu255, Asp256, Asp279, two substrate oxygens, and one water molecule. Tyr112 and Lys183 were identified as possible catalytic residues. Changes in tetramer organization were observed in different complexes, suggesting relevance for cooperative behavior and allosteric control. X-ray crystallography, structural analysis Nature structural biology High 10700286
2002 Crystal structure of ME2 in complex with ATP, Mn2+, tartronate, and fumarate (2.2 Å) showed that ATP acts as an active-site inhibitor despite the existence of an exo binding site. Fumarate binds at an allosteric site at the dimer interface, and mutations at this site abolished fumarate's activating effects, revealing the molecular mechanism of allosteric regulation by fumarate. X-ray crystallography, enzyme kinetics, site-directed mutagenesis Structure High 12121650
2009 ME2 enzymatic activity is present in pancreatic islets of humans, rats, mice, and INS-1 832/13 clonal insulinoma cells. ME2 uses either NAD or NADP as cofactor, has a high Km for malate, and is allosterically activated by fumarate and inhibited by ATP—properties distinguishing it from the cytosolic ME1 and mitochondrial ME3. Spectrophotometric enzyme activity assay, immunoblotting Archives of biochemistry and biophysics Medium 19691144
2013 p53 transcriptionally represses ME2 (and ME1) expression in human and mouse cells. ME2 downregulation reciprocally activates p53 through AMPK-mediated mechanisms in a feed-forward loop. Knockdown of ME2 induces cellular senescence (not apoptosis), while enforced ME2 expression suppresses senescence, establishing ME2 as a regulator of cell fate downstream of p53. Genetic knockdown/overexpression, epistasis analysis, cell senescence assays, metabolic measurements Nature High 23334421
2014 ME2 knockdown in A549 NSCLC cells inhibits cell proliferation, induces differentiation, increases ROS and NADP+/NADPH ratio, drops ATP, and increases cisplatin sensitivity. ME2 depletion reduces pyruvate and accumulates malate; exogenous membrane-permeable malate mimics this phenotype. ME2 knockdown also impacts PDK1/PTEN expression, leading to AKT inhibition. Both ME2 knockdown and malate treatment reduce tumor growth in vivo. shRNA knockdown, metabolic flux analysis (stable isotope tracing), in vivo xenograft, kinase signaling analysis Scientific reports High 24957098
2014 High-throughput screening identified NPD389 as a potent ME2 inhibitor (IC50 ~4.6 μM) that acts as an uncompetitive inhibitor with respect to NAD+ and a mixed-type inhibitor with respect to L-malate, indicating it binds at a site distinct from the active site (consistent with allosteric inhibition). High-throughput enzymatic screening, enzyme kinetics analysis, thermal shift assay Acta pharmacologica Sinica Medium 24681895
2015 The natural compound embonic acid (EA) is an allosteric inhibitor of ME2 with an IC50 of 1.4 μM. Mutagenesis and binding studies localized its binding site to the fumarate binding site or nearby dimer interface, distinct from the catalytic site (non-competitive inhibition). EA treatment and ME2 shRNA knockdown both inhibit H1299 cancer cell growth and induce cellular senescence via a p53-independent pathway. In vitro enzyme inhibition assays, site-directed mutagenesis, binding studies, shRNA knockdown, cellular senescence assays Oncotarget High 26008970
2017 Genomic deletion of ME2 in SMAD4-deleted pancreatic cancer creates collateral lethality upon depletion of its paralog ME3. Mechanistically, loss of mitochondrial malic enzymes (ME2 and ME3) diminishes NADPH production, elevates ROS, activates AMPK, which then directly suppresses SREBP1-directed transcription of BCAT2. Reduced BCAT2 impairs branched-chain amino acid transamination, depleting glutamate needed for nucleotide synthesis. Genetic depletion (shRNA/CRISPR), metabolomics, molecular epistasis, AMPK/SREBP1/BCAT2 pathway analysis Nature High 28099419
2021 ME2 promotes proneural-mesenchymal transition (PMT) and lipogenesis in glioblastoma by inhibiting mitochondrial ROS production and AMPK phosphorylation, resulting in SREBP-1 maturation and nuclear localization, which enhances the ACSS2 lipogenesis pathway. ME2 overexpression upregulates mesenchymal markers and inhibits proneural marker OLIG2. ME2 overexpression/knockdown, ROS measurement, AMPK/SREBP-1 signaling analysis, lipogenesis assays, migration/invasion assays Frontiers in oncology Medium 34381734
2023 SIRT5 physically interacts with ME2 and acts as its desuccinylase. Glutamine deprivation enhances the SIRT5-ME2 interaction, promoting SIRT5-mediated desuccinylation of ME2 at lysine 346, which activates ME2 enzymatic activity. Activated ME2 enhances mitochondrial respiration to counteract glutamine deprivation and support proliferation and tumorigenesis in colorectal cancer. Co-immunoprecipitation, succinylation assays, site-directed mutagenesis (K346), enzymatic activity assays, metabolic flux measurements, xenograft models Cell death and differentiation High 38007551
2023 ME2 promotes pyruvate production, which directly binds to β-catenin and increases β-catenin protein levels, thereby promoting hepatocellular carcinoma cell migration and invasion. Pyruvate treatment rescues migration in ME2-depleted cells, establishing the ME2→pyruvate→β-catenin axis. ME2 knockdown/overexpression, pyruvate supplementation rescue experiments, β-catenin protein level analysis, migration/invasion assays Metabolites Medium 37110198
2023 ME2 inhibition in AML cells (via ME2 silencing or allosteric inhibitor disodium embonate) decreases pyruvate and NADH, reducing ATP production via oxidative phosphorylation, and decreases NADPH, increasing ROS and oxidative stress, ultimately inducing apoptosis. ME2 silencing inhibits xenograft AML tumor growth in vivo. shRNA knockdown, allosteric inhibitor treatment, energy/redox metabolite measurements, xenograft in vivo models Cellular oncology Medium 37079187
2023 miR-214-3p directly targets ME2 (confirmed by dual luciferase reporter assay). In cardiomyocytes, miR-214-3p suppresses ME2 expression and promotes ferroptosis; ME2 overexpression ameliorates ferroptosis induced by miR-214-3p, while ME2 depletion compromises the protective effect of miR-214-3p inhibitor, establishing ME2 as a functional target of miR-214-3p in regulating ferroptosis during myocardial infarction. Dual luciferase reporter assay, miRNA mimic/inhibitor/antagomir, ME2 overexpression/knockdown, ferroptosis and iron accumulation assays, cardiac function measurement in mouse MI model Biochemical and biophysical research communications Medium 37087800
2024 AKT1 phosphorylates cytoplasmic ME2 (full-length isoform, ME2fl) at serine 9 within the mitochondrial localization signal, preventing its mitochondrial translocation. Cytoplasmic ME2fl acts as a scaffold assembling key glycolytic enzymes (PFKL, GAPDH, PKM2, LDHA) to promote glycolysis. This AKT1-driven phosphorylation induces a metabolic switch from mitochondrial TCA metabolism to glycolysis, enhancing glycolytic capacity of tumor cells in vitro and in vivo. In vitro phosphorylation assays, site-directed mutagenesis (S9), subcellular fractionation, co-immunoprecipitation of glycolytic enzyme complex, metabolic flux measurements, xenograft in vivo models Nature communications High 38263319
2024 ME2 is acetylated at lysine 156 by ACAT1. Decreased intracellular glucose triggers ACAT1-mediated K156 acetylation of ME2, potentiating its enzymatic activity and facilitating lactate production from glutamine. ME2-derived lactate promotes lactylation of homologous recombination repair proteins, contributing to chemotherapy resistance in ovarian cancer. ACAT1 inhibition reduces ME2 acetylation and chemoresistance in vitro and in vivo. Acetylation assays, site-directed mutagenesis (K156), co-immunoprecipitation, metabolomics, protein lactylation analysis, in vitro and in vivo chemoresistance assays Advanced science High 39951294
2024 PRMT1 interacts with ME2 and methylates ME2, activating its enzymatic activity. Mutation of ME2 at arginine 67 (R67K) mimics constitutive activation. PRMT1-mediated ME2 methylation increases mitochondrial respiration, promoting HCC cell proliferation and migration. PRMT1 inhibition reduces ME2 activity and tumor growth. Co-immunoprecipitation, site-directed mutagenesis (R67K), enzymatic activity assays, mitochondrial respiration measurements, cell proliferation/migration assays Cell death & disease Medium 39528487
2024 A homozygous frameshift variant in ME2 (c.1379_1380delTT, p.Phe460fs*22) produces truncated, unstable ME2 protein in vitro, causing ME2 deficiency associated with neurodevelopmental disorder, dilated cardiomyopathy, and mild lactic acidemia in a human patient. Deletion of the yeast ortholog of human ME2 causes growth arrest rescued by re-expression of human ME2, demonstrating ME2's essential role in mitochondrial function. Whole exome sequencing, in vitro protein expression/stability assay, yeast complementation assay Clinical genetics Medium 39401966
2025 CYP4F11 promotes ubiquitin-proteasomal degradation of ME2 when suppressed by miR-195, establishing a CYP4F11/miR-195/ME2 regulatory axis. CYP4F11 depletion disrupts mitochondrial malate metabolism, and ME2 rescue experiments confirm ME2 mediates the oncogenic metabolic effects of CYP4F11 in non-small cell lung cancer. 3'-UTR luciferase reporter assay, CYP4F11 knockdown, ME2 rescue experiments, metabolomic analysis, xenograft in vivo models Frontiers of medicine Medium 41359237

Source papers

Stage 0 corpus · 80 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2013 Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 407 23334421
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
2017 Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer. Nature 216 28099419
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2010 A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. The EMBO journal 153 20186120
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
2012 Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Molecular & cellular proteomics : MCP 145 22586326
2010 Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease. Molecular psychiatry 127 21116278
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2020 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Molecular cell 88 32707033
1985 Conjugal transfer from Streptococcus lactis ME2 of plasmids encoding phage resistance, nisin resistance and lactose-fermenting ability: evidence for a high-frequency conjugative plasmid responsible for abortive infection of virulent bacteriophage. Journal of general microbiology 88 3930657
1991 Human NAD(+)-dependent mitochondrial malic enzyme. cDNA cloning, primary structure, and expression in Escherichia coli. The Journal of biological chemistry 86 1993674
1998 EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction. Oncogene 82 9798675
2014 Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation. Cell reports 80 24981860
2017 A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III. Cell metabolism 78 28380382
2011 Me2-NHC based robust Ir catalyst for efficient water oxidation. Chemical communications (Cambridge, England) 73 21225028
2000 Structure of a closed form of human malic enzyme and implications for catalytic mechanism. Nature structural biology 73 10700286
2017 The PRMT5/WDR77 complex regulates alternative splicing through ZNF326 in breast cancer. Nucleic acids research 72 28977470
2014 Knockdown of malic enzyme 2 suppresses lung tumor growth, induces differentiation and impacts PI3K/AKT signaling. Scientific reports 72 24957098
2002 Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate. Structure (London, England : 1993) 68 12121650
2017 RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma. Leukemia 66 28186131
2022 Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery. Nature communications 65 35831314
2020 Proteome-wide identification of HSP70/HSC70 chaperone clients in human cells. PLoS biology 65 32687490
2004 Malic enzyme 2 may underlie susceptibility to adolescent-onset idiopathic generalized epilepsy. American journal of human genetics 65 15532013
1992 Molecular characterization of a second abortive phage resistance gene present in Lactococcus lactis subsp. lactis ME2. Journal of bacteriology 53 1429469
2023 SIRT5-mediated ME2 desuccinylation promotes cancer growth by enhancing mitochondrial respiration. Cell death and differentiation 50 38007551
2001 In vivo antitumor activity of bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) (METVAN [VO(SO4)(Me2-Phen)2]). Clinical cancer research : an official journal of the American Association for Cancer Research 47 11448932
1988 Restriction and modification activities from Streptococcus lactis ME2 are encoded by a self-transmissible plasmid, pTN20, that forms cointegrates during mobilization of lactose-fermenting ability. Journal of bacteriology 44 2841286
2008 Combination of 2-methoxyestradiol (2-ME2) and eugenol for apoptosis induction synergistically in androgen independent prostate cancer cells. The Journal of steroid biochemistry and molecular biology 40 19084597
1994 Expression of basic-helix-loop-helix transcription factor ME2 during brain development and in the regions of neuronal plasticity in the adult brain. Brain research. Molecular brain research 40 7984047
1998 The effect of Me2+ cofactors at the initial stages of V(D)J recombination. The Journal of biological chemistry 38 9632694
2003 2-Methoxyestradiol exhibits a biphasic effect on VEGF-A in tumor cells and upregulation is mediated through ER-alpha: a possible signaling pathway associated with the impact of 2-ME2 on proliferative cells. Neoplasia (New York, N.Y.) 34 14670179
2024 AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis. Nature communications 33 38263319
2015 Alkane metathesis with the tantalum methylidene [(≡SiO)Ta(═CH2)Me2]/[(≡SiO)2Ta(═CH2)Me] generated from well-defined surface organometallic complex [(≡SiO)Ta(V)Me4]. Journal of the American Chemical Society 32 25557135
1982 The structure of the EF-Tu . GDP . Me2+ complex. European journal of biochemistry 30 7200884
2015 Enhanced cytosolic NADP-ME2 activity in A. thaliana affects plant development, stress tolerance and specific diurnal and nocturnal cellular processes. Plant science : an international journal of experimental plant biology 29 26475199
1995 Differential expression and distinct DNA-binding specificity of ME1a and ME2 suggest a unique role during differentiation and neuronal plasticity. Brain research. Molecular brain research 27 7769987
2021 Plant defense compound triggers mycotoxin synthesis by regulating H2B ub1 and H3K4 me2/3 deposition. The New phytologist 26 34480757
2016 Sediment PAH source apportionment in the Liaohe River using the ME2 approach: A comparison to the PMF model. The Science of the total environment 26 26925728
2015 A small-molecule inhibitor suppresses the tumor-associated mitochondrial NAD(P)+-dependent malic enzyme (ME2) and induces cellular senescence. Oncotarget 24 26008970
2025 ACAT1-Mediated ME2 Acetylation Drives Chemoresistance in Ovarian Cancer by Linking Glutaminolysis to Lactate Production. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 23 39951294
2023 Inhibition of miR-214-3p attenuates ferroptosis in myocardial infarction via regulating ME2. Biochemical and biophysical research communications 22 37087800
2021 ME2 Promotes Proneural-Mesenchymal Transition and Lipogenesis in Glioblastoma. Frontiers in oncology 20 34381734
2017 Miz1 Controls Schwann Cell Proliferation via H3K36me2 Demethylase Kdm8 to Prevent Peripheral Nerve Demyelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 18 29217679
2014 Discovery of a novel inhibitor of NAD(P)(+)-dependent malic enzyme (ME2) by high-throughput screening. Acta pharmacologica Sinica 18 24681895
2009 Mitochondrial malic enzyme (ME2) in pancreatic islets of the human, rat and mouse and clonal insulinoma cells. Archives of biochemistry and biophysics 18 19691144
1976 Me2+-(13 S) ATPase from Micrococcus sp. ATCC 398E. The effect of trypsin on the purified enzyme. Biochimica et biophysica acta 15 131581
2006 Innovative effect of illite on improved microbiological conversion of L-tyrosine to 3,4 dihydroxy phenyl L-alanine (L-DOPA) by Aspergillus oryzae ME2 under acidic reaction conditions. Current microbiology 13 17039388
2001 Apoptosis inducing novel anti-leukemic agent, bis(4,7-dimethyl-1,10 phenanthroline) sulfatooxovanadium(IV) [VO(SO4)(Me2-Phen)2] depolarizes mitochondrial membranes. Leukemia & lymphoma 13 11378580
1985 Linkage between the loci for mitochondrial malic enzyme (ME2) and coagulation factor XIIIA subunit (F13A). Human genetics 13 2860058
2015 Implementing constrained multi-time approach with bootstrap analysis in ME-2: An application to PM2.5 data from Florence (Italy). The Science of the total environment 12 26414851
2023 Targeting human mitochondrial NAD(P)+-dependent malic enzyme (ME2) impairs energy metabolism and redox state and exhibits antileukemic activity in acute myeloid leukemia. Cellular oncology (Dordrecht, Netherlands) 10 37079187
2016 The level and distribution pattern of HP1β in the embryonic brain correspond to those of H3K9me1/me2 but not of H3K9me3. Histochemistry and cell biology 7 26794325
2014 Dynamic effects dictate the mechanism and selectivity of dehydration-rearrangement reactions of protonated alcohols [Me2 (R)CCH(OH2 )Me](+) (R=Me, Et, iPr) in the gas phase. Chemistry (Weinheim an der Bergstrasse, Germany) 7 25179304
2023 Cucumber malate decarboxylase, CsNADP-ME2, functions in the balance of carbon and amino acid metabolism in fruit. Horticulture research 5 38077499
2022 Study on the Effect of Key Genes ME2 and adhE during Luzhou-Flavor Baijiu Brewing. Foods (Basel, Switzerland) 5 35267332
1982 Induction of 2H+/Me2+ exchange in rat-liver mitochondria. European journal of biochemistry 5 6293824
2024 NADP-malic Enzyme OsNADP-ME2 Modulates Plant Height Involving in Gibberellin Signaling in Rice. Rice (New York, N.Y.) 4 39152344
2019 Genome-wide identification of histone methylation (H3K9me2) and acetylation (H4K12ac) marks in two ecotypes of switchgrass (Panicum virgatum L.). BMC genomics 4 31438854
2015 Metabolic vulnerability in melanoma: a ME2 (me too) story. The Journal of investigative dermatology 4 25666673
2003 Xstir polymorphism and absence of sex linkage in Xenopus laevis ME2 gene. Folia biologica 4 12859020
2024 ME2 Deficiency Is Associated With Recessive Neurodevelopmental Disorder. Clinical genetics 3 39401966
2024 PRMT1-mediated methylation of ME2 promotes hepatocellular carcinoma growth by inhibiting ubiquitination. Cell death & disease 3 39528487
2023 ME2 Promotes Hepatocellular Carcinoma Cell Migration through Pyruvate. Metabolites 3 37110198
2018 Preparation and Properties of Nanoparticles, tRNA-Bivalent Metal Cation (Me2+) Complexes, and Prospects of Their Practical Use. Doklady. Biochemistry and biophysics 3 29779113
2013 (N,N-diethyldithiocarbamato)[tris(3,5-dimethylpyrazol-1-yl)hydroborato]copper(II): a new copper(II) dithiocarbamate compound with the classic Tp(Me2) scorpionate. Acta crystallographica. Section C, Crystal structure communications 1 24005503
2025 CYP4F11 promotes lung cancer progression through the miR-195/ME2 pathway. Frontiers of medicine 0 41359237
2024 A Targeted Octahedral DNA Nanostructure Co-delivers siME3 and Doxorubicin to Enhance Collateral Lethality in ME2-Deficient Pancreatic Cancer. Nano letters 0 39602246
2015 Long-term remission of therapy-related acute myeloid leukemia with a new t(11;18)(q23;q21.2) translocation and KMT2A-ME2 (MLL-ME2) fusion gene. Cancer genetics 0 26556690
2014 Competitive reaction pathways for the gas-phase reactivity of [Me2 AlNH2 ]3. Chemphyschem : a European journal of chemical physics and physical chemistry 0 24976567
1990 A population study of leukocyte enzymes (GOT2, ME2 and PGM3) in Galicia (NW Spain). Human heredity 0 2138119