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Showing SLC16A7 — MCT2 is a alias.

SLC16A7

Monocarboxylate transporter 2 · UniProt O60669

Length
478 aa
Mass
52.2 kDa
Annotated
2026-06-10
70 papers in source corpus 32 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC16A7/MCT2 is a high-affinity, proton-coupled monocarboxylate transporter that moves pyruvate, lactate, and ketone bodies across membranes to support cellular energy metabolism (PMID:7829520, PMID:10417314, PMID:9786900). It distinguishes itself from other MCTs by its high substrate affinity (lactate Km ~0.74 mM; pyruvate Km ~25 µM) and by its insensitivity to organomercurial thiol reagents (PMID:10417314, PMID:9786900), a property explained by its preferential association with the ancillary protein embigin (gp70) rather than basigin/CD147 for plasma-membrane expression (PMID:15917240); neuroplastins serve this chaperone role in neural tissue, and basigin substitutes in spermatozoa, indicating cell-type-specific ancillary partnerships (PMID:24260123, PMID:21792931). The ancillary protein modulates inhibitor sensitivity and surface delivery, while the transmembrane domains (TM7–12) set substrate affinity; the small-molecule inhibitor AR-C155858 binds an intracellular site formed by TMs 7–10, and extracellular carbonic anhydrase IV non-catalytically augments transport when embigin is present (PMID:19929853, PMID:20695846, PMID:21680735). In neurons, MCT2 is a postsynaptic density protein at glutamatergic synapses that co-distributes and co-traffics with AMPA receptor GluR2/3 subunits and PICK1, with surface delivery tied to neuronal lactate uptake and its protein levels controlled translationally through the PI3K–Akt–mTOR–S6K pathway downstream of insulin/IGF-1 and noradrenaline (PMID:11291733, PMID:15749979, PMID:19453627, PMID:18093179, PMID:17394554, PMID:19457092). Neuronal MCT2-mediated lactate transport is required for activity-dependent metabolic and hemodynamic responses, angiogenesis, hypothalamic satiety signaling, and is neuroprotective in retinal and myelin contexts (PMID:28388627, PMID:40032881, PMID:41046267, PMID:32422282). In prostate cancer, MCT2 is redirected to peroxisomes via interaction with Pex19, where its peroxisomal localization supports β-oxidation and is required for proliferation, and its overexpression is driven by demethylation of an internal SLC16A7 promoter (PMID:25639644, PMID:33121137, PMID:26035357). MCT2 also governs the intracellular delivery and consequent activity of the small-molecule methyloxalylglycine, dictating its metabolic and cytotoxic mode of action (PMID:30297875, PMID:36028752). No Mendelian disease link is established in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Establishing the core identity of MCT2 required showing it is a proton-coupled monocarboxylate transporter, which defined its basic transport function and substrate selectivity.

    Evidence Heterologous expression in Sf9 insect cells and Xenopus oocytes with radiolabeled transport and pharmacological inhibition; cDNA cloning and FISH mapping to 12q13

    PMID:10417314 PMID:7829520 PMID:9786900

    Open questions at the time
    • No structural model of the transporter resolved
    • Stoichiometry of H+/monocarboxylate coupling not fully defined in these studies
  2. 1999 High

    Quantitative kinetics established MCT2 as a high-affinity transporter (~10-fold higher affinity than MCT1) with a broad ketone-body/branched-keto-acid substrate range, explaining its niche in tissues requiring efficient low-substrate uptake.

    Evidence Xenopus oocyte radiolabeled transport assays with multiple substrates and inhibition kinetics

    PMID:10417314

    Open questions at the time
    • Tissue-level relevance of each substrate not addressed
    • Does not distinguish import vs export directionality in vivo
  3. 2005 High

    Identifying embigin rather than basigin as the obligate ancillary protein answered how MCT2 reaches the plasma membrane and mechanistically explained its distinct pharmacology (pCMBS insensitivity).

    Evidence Co-immunoprecipitation, FRET with CFP/YFP-tagged proteins, and site-directed mutagenesis of CD147

    PMID:15917240

    Open questions at the time
    • Stoichiometry of MCT2-embigin complex not defined
    • Did not test whether embigin is universally required across all tissues
  4. 2010 High

    Mapping the AR-C155858 binding site and showing the ancillary protein modulates inhibitor sensitivity defined which protein domains govern transport versus drug response, separating substrate affinity (TM domains) from inhibitor sensitivity (ancillary-dependent).

    Evidence Xenopus oocyte expression with chimeric/truncation constructs, microinjection, ancillary protein swaps, and inhibitor titrations

    PMID:19929853 PMID:20695846

    Open questions at the time
    • No co-crystal structure of inhibitor bound
    • Conformational mechanism of ancillary modulation unresolved
  5. 2011 High

    Demonstrating that extracellular carbonic anhydrase IV augments MCT2 transport non-catalytically revealed a regulatory partner that boosts flux independent of pH-buffering enzymatic activity.

    Evidence Xenopus oocyte co-expression with catalytically inactive CAIV mutants and pharmacological inhibition of CA activity

    PMID:21680735

    Open questions at the time
    • Physiological context of CAIV-MCT2 interaction not established in native tissue
    • Molecular interaction surface between CAIV and the MCT2-embigin complex undefined
  6. 2013 High

    Identifying neuroplastins as MCT2 ancillary proteins explained how MCT2 achieves surface expression in neural tissue where embigin distribution may be limited.

    Evidence COS-7 co-transfection, Xenopus oocyte antisense knockdown, immunocytochemistry, and lactate transport assays

    PMID:24260123

    Open questions at the time
    • Relative contribution of neuroplastin vs embigin in individual neuron types not quantified
    • Whether neuroplastin alters inhibitor sensitivity not tested
  7. 2009 High

    Defining MCT2 as a postsynaptic density protein that physically and functionally co-traffics with AMPA receptor GluR2/3 and PICK1 connected lactate transport to activity-dependent synaptic delivery and metabolic support of excitatory neurons.

    Evidence Immunogold EM, reciprocal co-IP, surface biotinylation, parallel trafficking experiments, and fluorescent lactate flux assays

    PMID:11291733 PMID:15749979 PMID:19453627 PMID:19457092

    Open questions at the time
    • Whether MCT2 trafficking is causally required for AMPA receptor trafficking versus co-regulated unresolved
    • Functional consequence of vesicular MCT2 pool not directly measured
  8. 2007 Medium

    Showing MCT2 protein is upregulated translationally via PI3K-Akt-mTOR-S6K by noradrenaline, insulin, IGF-1, and BDNF established that neuronal MCT2 abundance is a tunable, signal-responsive node rather than transcriptionally fixed.

    Evidence Western blot with mRNA/protein dissociation, selective pathway inhibitors, and in vivo BDNF injection with immunohistochemistry

    PMID:17394554 PMID:18093179 PMID:21736920

    Open questions at the time
    • No genetic rescue to confirm pathway specificity
    • Direct mRNA targets/translational control elements not identified
  9. 2015 Medium

    Discovery of peroxisomal MCT2 localization via Pex19 in prostate cancer revealed an organelle-specific role distinct from plasma-membrane transport, linking MCT2 to β-oxidation and malignant proliferation.

    Evidence Co-localization with peroxisomal markers, co-IP with Pex19, localization-variant rescue of proliferation, bisulfite methylation analysis, and ChIP for AR/ERG

    PMID:25639644 PMID:26035357 PMID:33121137

    Open questions at the time
    • Substrate transported by peroxisomal MCT2 not directly demonstrated
    • Mechanism connecting peroxisomal transport to proliferation undefined
    • Whether embigin/ancillary protein participates in peroxisomal targeting unknown
  10. 2018 High

    Showing MCT2 controls cellular uptake of methyloxalylglycine and thereby dictates its metabolic mode of action established MCT2 as a determinant of small-molecule pharmacology and intracellular drug concentration.

    Evidence LC-MS metabolomics, MCT2 KD/KO, transport assays, respiration assays, and SAR with MOG analogues

    PMID:30297875 PMID:36028752

    Open questions at the time
    • Generality to other monocarboxylate-mimetic drugs not established
    • Native physiological substrate competition with such drugs not quantified
  11. 2017 Medium

    Demonstrating transcriptional control of MCT2 by Notch/Hes1 and β-catenin, and lactate-mediated c-Jun stabilization, placed MCT2 within signaling networks where lactate import acts as a metabolic and signaling input.

    Evidence ChIP for Hes1 and β-catenin at the MCT2 locus, LC-MS lactate-c-Jun interaction, CRISPR-Cas9 KO, and DARTS/CETSA

    PMID:35263597 PMID:40915373

    Open questions at the time
    • Direct lactate-c-Jun binding mode not structurally resolved
    • Cell-type generality of β-catenin/c-Myc/MCT2 axis not established
  12. 2019 High

    In vivo neuronal MCT2 knockdown studies established that MCT2-mediated lactate transport is functionally required for activity-dependent metabolic responses, neurovascular coupling, angiogenesis, satiety signaling, and neuroprotection.

    Evidence Lentiviral/AAV shRNA and conditional KO with NMR/13C-labeling, fMRI, RNA-seq, feeding behavior, ERG, and enzyme/ATP assays across cortex, hypothalamus, retina, and oligodendrocytes

    PMID:28388627 PMID:32422282 PMID:40032881 PMID:40178895 PMID:41046267

    Open questions at the time
    • Quantitative contribution of MCT2 versus other MCTs in each tissue not fully isolated
    • Whether transport per se or protein-protein scaffolding drives some phenotypes unresolved
  13. 2025 Medium

    Cell-type-specific MCT2 deletion and pharmacological blockade refined when lactate transport is dispensable versus essential, showing it is required for myelin maintenance and lactate-only-fueled oscillations but not for glucose-supported synaptic transmission.

    Evidence Oligodendrocyte conditional KO with ketogenic-diet rescue and human MS tissue analysis; LFP recordings with AR-C155858 and FRET lactate sensors

    PMID:41048117

    Open questions at the time
    • Oligodendrocyte KO finding is from a preprint not yet peer-reviewed
    • Mechanism linking MCT2 loss to lipid-synthesis enzyme downregulation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MCT2 is sorted between plasma membrane, peroxisomes, and mitochondria in different cell types, and what governs the choice of ancillary partner, remains the central unresolved question.
  • No structural basis for substrate selectivity or organelle targeting
  • Mechanism dictating embigin vs neuroplastin vs basigin choice unknown
  • Direct demonstration of peroxisomal/mitochondrial transport substrate lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0140104 molecular carrier activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005777 peroxisome 3 GO:0031410 cytoplasmic vesicle 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1430728 Metabolism 4 R-HSA-382551 Transport of small molecules 3
Partners
AQP9BSGCA4EMBGRIA2NPTNPEX19PICK1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 MCT2 (SLC16A7) transports pyruvate and lactate in a proton-coupled manner; it is sensitive to phloretin and alpha-cyano-4-hydroxycinnamate but insensitive to organomercurial thiol reagents (e.g., p-chloromercuribenzoic acid), distinguishing it from MCT1. Functional activity was demonstrated by expression in Sf9 insect cells using recombinant baculovirus vectors. Heterologous expression in Sf9 insect cells (baculovirus), transport assays, pharmacological inhibition, immunoblotting/immunofluorescence The Journal of biological chemistry High 7829520
1999 MCT2 is a high-affinity H+/monocarboxylate transporter with Km ~0.74 mM for lactate at pH 7.0 (approximately 10-fold higher affinity than MCT1). Substrates include lactate, pyruvate, β-hydroxybutyrate, acetoacetate, and branched-chain keto acids. Transport is driven by the H+ gradient and is inhibited by alpha-cyano-4-hydroxycinnamate, anion-channel inhibitors, and flavonoids. Heterologous expression in Xenopus laevis oocytes, radiolabeled transport assays, inhibition kinetics The Biochemical journal High 10417314
1998 Human MCT2 (SLC16A7) is a high-affinity pyruvate transporter with an apparent Km of ~25 µM for pyruvate, functioning as a H+/monocarboxylate cotransporter. The gene maps to chromosome 12q13. cDNA cloning, heterologous expression, kinetic transport assays, fluorescence in situ hybridization The Journal of biological chemistry High 9786900
2005 MCT2 associates with the ancillary protein embigin (gp70) rather than basigin (CD147) for plasma membrane expression, in contrast to MCT1 and MCT4 which associate with basigin. This interaction was confirmed by co-immunoprecipitation and FRET between CFP/YFP-tagged MCT2 and gp70. The MCT2-embigin association explains the insensitivity of MCT2 to pCMBS inhibition, because pCMBS targets the disulfide bridge in the Ig-like C2 domain of CD147. Co-immunoprecipitation, FRET (CFP/YFP-tagged proteins), site-directed mutagenesis of CD147, cell-impermeant organomercurial inhibitor assays The Journal of biological chemistry High 15917240
2010 AR-C155858 is a potent inhibitor of MCT2 (and MCT1) that binds to an intracellular site involving transmembrane helices 7–10. Inhibition is time-dependent and the compound is active when microinjected, confirming intracellular binding. MCT4 is not inhibited. Chimeric transporter experiments localized the binding site to the C-terminal half of MCT1 (and by extension MCT2). Xenopus oocyte expression, inhibitor titrations, microinjection, chimeric MCT1/MCT4 constructs, Km determination The Biochemical journal High 19929853
2010 The ancillary protein associated with MCT2 modulates its sensitivity to AR-C155858: MCT2 expressed with endogenous Xenopus basigin is potently inhibited by AR-C155858, whereas MCT2 co-expressed with exogenous embigin is insensitive to AR-C155858. Embigin modulates MCT2 inhibitor sensitivity through interactions with the intracellular C-terminus and TMs 3 and 6. Lactate Km is determined primarily by the TM domains (TM7–12) of MCT2 and not by the associated ancillary protein. Xenopus oocyte expression, co-expression of embigin/basigin, chimeric and truncation constructs, inhibitor titrations, RT-PCR The Biochemical journal High 20695846
2011 Extracellular membrane-bound carbonic anhydrase IV (CAIV), but not cytosolic CAII, enhances transport activity of MCT2. CAIV augmentation of MCT2 is independent of CAIV catalytic activity (shown by ethoxyzolamide treatment and catalytically inactive CAIV-V165Y mutant) and does not require its intramolecular H+-shuttle residue His-88. Enhancement only occurs when MCT2 is co-expressed with its ancillary protein embigin (gp70). Xenopus oocyte co-expression, pharmacological inhibition, site-directed mutagenesis of CAIV, electrophysiological transport assays The Journal of biological chemistry High 21680735
2013 Neuroplastins (np65 and np55), Ig superfamily adhesion molecules, act as ancillary proteins for MCT2, enabling its plasma membrane expression and lactate transport activity. Demonstrated by co-transfection in COS-7 cells, knockdown of endogenous Xenopus neuroplastin reducing MCT2 surface expression and transport, and co-localization of MCT2 and neuroplastins in rat cerebellum (parasagittal zebrin II-negative stripes). Co-transfection in COS-7 cells, Xenopus oocyte antisense RNA knockdown, immunocytochemistry, lactate transport assays PloS one High 24260123
2001 MCT2 is concentrated at postsynaptic densities of parallel fiber–Purkinje cell synapses in cerebellum, co-localizing with delta2 glutamate receptors, as shown by immunogold electron microscopy. This identifies MCT2 as a novel postsynaptic density protein. Confocal immunofluorescence microscopy, double-labeling immunogold electron microscopy Experimental brain research High 11291733
2005 MCT2 is selectively localized at postsynaptic densities of asymmetric (glutamatergic) synapses in hippocampal CA1 and CA3 and cerebellar parallel fiber–Purkinje cell synapses. MCT2 co-distributes quantitatively with AMPA receptor GluR2/3 subunits within postsynaptic densities. A significant intracellular vesicular pool of MCT2 exists within postsynaptic spines, suggesting endo/exocytotic trafficking analogous to AMPA receptors. Post-embedding electron microscopic immunocytochemistry, quantitative double-labeling immunogold Cerebral cortex High 15749979
2009 MCT2 co-immunoprecipitates with AMPA receptor GluR2/3 subunits and the GluR2/3-interacting protein PICK1 (C-kinase-interacting protein 1) in neurons, indicating a close physical interaction within dendritic spines. MCT2 and GluR2/3 undergo parallel membrane trafficking: AMPA or insulin stimulation causes intracellular accumulation of both, while TNF-α and glycine/glutamate increase their cell-surface expression. Surface translocation of MCT2 is associated with enhanced neuronal lactate uptake. Co-immunoprecipitation, immunofluorescence co-localization, cell-surface biotinylation, Western blot on membrane/cytoplasm fractions, fluorescent lactate flux assay The European journal of neuroscience High 19453627
2009 MCT2 protein expression in cultured cortical neurons is upregulated by insulin and IGF-1 through a translational (not transcriptional) mechanism requiring the PI3K–Akt–mTOR–S6K pathway. mTOR inhibitor rapamycin and PI3K inhibitor LY294002 almost completely blocked MCT2 protein upregulation, whereas MEK inhibitor PD98059 had no effect. The increase in MCT2 protein occurred in an intracellular pool without change at the cell surface. Western blot, qRT-PCR (no mRNA change), pharmacological pathway inhibitors, immunocytochemistry for subcellular localization The European journal of neuroscience Medium 18093179
2007 Noradrenaline (NA) increases neuronal MCT2 protein expression via translational activation through the PI3K/Akt and mTOR/S6K pathway. LY294002 and rapamycin almost completely blocked NA-induced MCT2 upregulation, whereas MEK and p38 MAPK inhibitors had smaller effects. NA did not significantly alter MCT2 mRNA levels, confirming post-transcriptional regulation. Western blot, qRT-PCR, pharmacological inhibitors (LY294002, rapamycin, PD98059, SB202190), phosphorylation analyses Journal of neurochemistry Medium 17394554
2009 MCT2 co-immunoprecipitates with AQP9 (aquaglyceroporin) from hippocampal neuron homogenates, and both proteins co-localize in mitochondria of hippocampal neurons. Glutamate exposure enhances protein (but not mRNA) expression of both MCT2 and AQP9 in these neurons. Co-immunoprecipitation, immunofluorescence co-localization, Western blot, qRT-PCR Frontiers in neuroscience Medium 25161606
2012 In murine spermatozoa, basigin (CD147) co-localizes and co-immunoprecipitates with both MCT1 and MCT2, whereas embigin interaction was not detectable. This differs from somatic cells where MCT2 preferentially associates with embigin. MCT-mediated L-lactate transport (measured as pHi decrease) in sperm was blocked by alpha-cyano-4-OH cinnamate. Co-immunoprecipitation, immunofluorescence co-localization, intracellular pH measurement with fluorescent dye, ATP assay Journal of cellular physiology Medium 21792931
2018 MCT2 mediates cellular uptake of methyloxalylglycine (MOG), the hydrolysis product of DMOG. MCT2-facilitated entry of MOG into cells leads to sufficiently high intracellular concentrations of NOG to inhibit glutamate dehydrogenase and other glutamine metabolism enzymes, suppress mitochondrial respiration, decrease TCA-cycle flux from glutamine, and reduce ATP production, causing cytotoxicity in an MCT2-dependent manner. LC-MS metabolomics, MCT2 KD/KO, transport assays, mitochondrial respiration assays, cell viability assays Nature chemical biology High 30297875
2022 MOG analogues that maintain MCT2-dependent cell entry but do not inhibit glutaminolysis or cause cytotoxicity were identified, functionally mapping the MCT2 pharmacophore. These compounds can still inhibit PHDs, allowing uncoupling of glutaminolysis from PHD activity and demonstrating that MCT2 dictates the mode of action of NOG by controlling its intracellular concentration. Structure-activity relationship with MOG analogues, cell viability assays, metabolic flux assays, MCT2-expressing cell lines Communications biology Medium 36028752
2022 Notch/RBP-J signaling represses MCT2 transcription via its downstream effector Hes1, reducing intracellular lactate levels in myeloid cells. Reduced MCT2-mediated lactate import blunts granulocytic MDSC differentiation and promotes TAM maturation. Lactate (transported via MCT2) was identified to interact with and stabilize c-Jun protein against FBW7 ubiquitin-ligase-mediated degradation, using LC-MS and CRISPR-Cas9 gene disruption. Chromatin immunoprecipitation (Hes1 at MCT2 locus), LC-MS (lactate-c-Jun interaction), CRISPR-Cas9 KO, flow cytometry, Western blot Cell reports Medium 35263597
2009 MCT2 regulation of GluR2 AMPA receptor subcellular distribution was demonstrated: co-expression of MCT2 with GluR2-Venus in Neuro2A cells and cortical neurons caused GluR2 to redistribute into perinuclear and dendritic clusters following MCT2 distribution. MCT2 co-expression reduced both cell-surface and total GluR2 protein levels. MCT2 partially co-localized with Rab8 in dendrites, suggesting involvement in AMPA receptor membrane trafficking. Fluorescence microscopy with mStrawberry-MCT2 and Venus-GluR2 co-transfection, cell-surface biotinylation, Western blot Journal of neurochemistry Medium 19457092
2017 Neuronal MCT2 knockdown (~25%) in rat somatosensory cortex using lentiviral shRNA abrogated the activity-dependent increase in lactate content observed during whisker stimulation (measured by HRMAS 1H-NMR and in vivo 1H-NMR). MCT2 KD also attenuated TCA cycle velocity increase upon activation and abolished the BOLD fMRI response to whisker stimulation. 13C-labeling confirmed that elevated lactate during activation originates from newly synthesized glucose-derived lactate. Lentiviral shRNA KD, HRMAS 1H-NMR spectroscopy, 13C-NMR with [1-13C]glucose infusion, in vivo 1H-NMR, BOLD fMRI PloS one High 28388627
2015 MCT2 localizes predominantly to peroxisomes in prostate cancer (PCa) cells, interacting with the peroxisomal membrane protein Pex19 to exploit the peroxisomal import machinery. This peroxisomal localization correlates with increased peroxisomal β-oxidation activity and is associated with malignant transformation. Immunofluorescence co-localization with peroxisomal markers, co-immunoprecipitation with Pex19, Western blot, immunohistochemistry Journal of cellular and molecular medicine Medium 25639644
2020 Peroxisomal localization of MCT2 is required for PCa cell proliferation: MCT2 knock-down reduced PCa cell growth, and re-expression of MCT2 variants unable to localize to peroxisomes did not rescue proliferation, whereas peroxisome-targeted MCT2 did. siRNA knockdown, rescue with localization-variant constructs, proliferation assays Cancers Medium 33121137
2015 Epigenetic demethylation of an internal SLC16A7/MCT2 promoter is a recurrent event in prostate cancer, driving expression of isoforms differing in 5'-UTR translational control motifs, contributing to MCT2 protein overexpression. Androgen receptor (AR) and ERG transcription factors bind at the SLC16A7 locus. MCT2 knockdown attenuated PCa cell growth. Bisulfite sequencing (methylation), integrative transcriptomic/epigenomic analysis, ChIP (AR/ERG), siRNA knockdown, cell proliferation assay Oncotarget Medium 26035357
2003 MCT2 expression in spermatid tails is developmentally regulated, appearing at postnatal day 18 in elongating spermatids. MCT2 mRNA levels in testis are negatively regulated by FSH and testosterone (both reducing MCT2 mRNA in a dose-dependent manner in isolated seminiferous tubules), and also by TNF-α and TGF-β. Hypophysectomy caused an 8-fold increase in testicular MCT2 mRNA, reversed by FSH or LH administration. Northern blot, Western blot, immunoelectron microscopy, in vitro seminiferous tubule incubation with hormones, hypophysectomy model Biology of reproduction Medium 12773420
2008 In preimplantation mouse embryos, SLC16A7 (MCT2) protein localizes to apical cortical regions and vesicular/peroxisomal compartments (partially co-localizing with peroxisomal catalase), distinct from plasma membrane localization of MCT4. SLC16A7 expression is upregulated in the absence of glucose, in contrast to MCT1 and MCT4 which require glucose, suggesting a unique role in peroxisomal redox regulation. Immunofluorescence localization, co-localization with peroxisomal catalase, Western blot, mRNA analysis under varying glucose conditions Biology of reproduction Medium 18385447
2011 BDNF injection into mouse hippocampal CA1 area enhanced MCT2 protein expression in vivo (confirmed by immunohistochemistry and immunoblot), co-occurring with upregulation of postsynaptic plasticity proteins PSD95 and GluR2 but not glial MCT1/MCT4, synaptic vesicle proteins, or αCaMKII. This places MCT2 upregulation in the context of BDNF-mediated synaptic plasticity. Intrahippocampal BDNF injection, immunohistochemistry, Western blot Neuroscience Medium 21736920
2020 AAV2-mediated overexpression of MCT2 in retinal ganglion cells (RGCs) of two glaucoma models preserved RGC density, axon number, and function (pattern ERG), reduced energy imbalance, and increased mitochondrial function (cytochrome c oxidase and succinate dehydrogenase activity). Conditional reduction of MCT2 in RGCs via AAV2-Cre in MCT2fl/+ mice caused significant decline in ATP production and visual evoked potential. AAV2-GFP-MCT2 intraocular injection, AAV2-Cre conditional KO, pattern ERG, RGC density quantification, enzyme activity assays (COX, SDH), ATP measurement Neurobiology of disease High 32422282
2025 Deletion of MCT2 specifically in oligodendrocytes did not affect oligodendrocyte survival but resulted in downregulation of lipid synthesis-associated enzymes and failure of myelin maintenance. Concomitant axonal upregulation of lactate dehydrogenase A and axonal damage were observed. Ketogenic diet alleviated the axonal damage phenotype. MCT2 is expressed by myelinating oligodendrocytes in both mice and humans and is downregulated in progressive multiple sclerosis. Conditional KO in oligodendrocytes, immunohistochemistry, enzyme expression analysis, ketogenic diet intervention, human MS tissue analysis bioRxivpreprint Medium
2025 AAV-mediated expression of MCT2 in retinal pigment epithelium (RPE) cells promoted cone survival and function in rat and mouse retinitis pigmentosa models. FLIM biosensors showed changes in lactate and glucose levels within MCT2-expressing RPE, suggesting MCT2 in RPE promotes lactate uptake from blood, alters RPE metabolism, and increases glucose availability to cones. AAV gene delivery to RPE, ERG and visual function testing, fluorescence lifetime imaging (FLIM) biosensors for lactate and glucose in vivo Proceedings of the National Academy of Sciences of the United States of America Medium 40178895
2025 MCT2 knockdown in arcuate nucleus neurons of female rats (via AAV-shRNA) significantly increased food intake and body weight after fasting/refeeding, demonstrating that neuronal MCT2-mediated lactate transport in hypothalamic arcuate nucleus is required for normal satiety signaling. MCT2 KD also led to compensatory inhibition of MCT1, suggesting glial adaptation to increased parenchymal lactate. AAV-shRNA knockdown in arcuate nucleus, real-time PCR, Western blot, immunohistochemistry, feeding behavior analysis (macro/microstructure) Scientific reports Medium 40032881
2025 Lactate transport via neuronal MCT2 is not required for sustained synchronized synaptic transmission (gamma oscillations or sharp wave-ripples) in hippocampal slices supplied with glucose. MCT1/2 blockade by AR-C155858 did not affect gamma oscillation properties when glucose was the energy supply, but fully suppressed oscillations when lactate was the sole substrate. Intracellular lactate accumulation in neurons upon MCT1/2 blockade was confirmed by FRET sensor imaging. Local field potential recordings, pharmacological MCT1/2 blockade (AR-C155858), UPLC-MS lactate measurement, FRET (Laconic sensor) imaging in neuron-astrocyte cultures Journal of neurochemistry Medium 41048117
2025 β-catenin directly binds to and transcriptionally activates the MCT2 promoter (confirmed by ChIP-qPCR with JASPAR motif prediction). β-catenin overexpression markedly increased MCT2 mRNA and protein. The β-catenin/c-Myc/MCT2 signaling axis regulates mitochondrial energy metabolism; gastrodin stabilizes β-catenin protein (confirmed by DARTS and CETSA), increasing MCT2 expression and pyruvate/ATP levels in AD models. ChIP-qPCR (β-catenin at MCT2 promoter), lentiviral β-catenin overexpression, Western blot, qPCR, DARTS, CETSA, ATP/pyruvate assays Journal of ethnopharmacology Medium 40915373
2025 Neuronal MCT2 is required for WS (whisker stimulation)-induced angiogenesis in neonatal mouse neocortex. MCT2 facilitates L-lactate influx into cortex, promoting lactate uptake by neurons and astrocytes, which activates HIF1α and VEGFa expression in astrocytes, driving angiogenesis. Neuronal MCT2 loss-of-function abolished these angiogenic and metabolic responses. RNA-seq, RNA-scope spatial transcriptomics, genetic loss-of-function, lactate measurements, immunofluorescence for VEGFa/HIF1α, vascular density quantification Cell death and differentiation Medium 41046267

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1. The Journal of biological chemistry 294 7829520
2005 Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4: the ancillary protein for the insensitive MCT2 is EMBIGIN (gp70). The Journal of biological chemistry 255 15917240
1999 Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. The Biochemical journal 242 10417314
2010 AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7-10. The Biochemical journal 208 19929853
2000 Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy. Neuroscience 199 11098125
2003 Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain. Neuroscience 181 14622911
1998 Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter. The Journal of biological chemistry 175 9786900
2002 MCT2 is a major neuronal monocarboxylate transporter in the adult mouse brain. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 163 11973431
2009 Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes. Pflugers Archiv : European journal of physiology 137 19876643
2001 A novel postsynaptic density protein: the monocarboxylate transporter MCT2 is co-localized with delta-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses. Experimental brain research 134 11291733
1997 Cloning of the monocarboxylate transporter isoform MCT2 from rat testis provides evidence that expression in tissues is species-specific and may involve post-transcriptional regulation. The Biochemical journal 122 9182702
1998 Expression of the monocarboxylate transporter MCT2 by rat brain glia. Glia 106 9482213
2000 Monocarboxylic acid transporters, MCT1 and MCT2, in cortical astrocytes in vitro and in vivo. American journal of physiology. Cell physiology 102 10794666
2014 Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins. Journal of applied physiology (Bethesda, Md. : 1985) 93 24610532
2009 Enhanced cerebral expression of MCT1 and MCT2 in a rat ischemia model occurs in activated microglial cells. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 92 19401710
2005 Selective postsynaptic co-localization of MCT2 with AMPA receptor GluR2/3 subunits at excitatory synapses exhibiting AMPA receptor trafficking. Cerebral cortex (New York, N.Y. : 1991) 91 15749979
1999 Distribution of monocarboxylate transporters MCT1 and MCT2 in rat retina. Neuroscience 91 10392858
2022 Notch-mediated lactate metabolism regulates MDSC development through the Hes1/MCT2/c-Jun axis. Cell reports 85 35263597
2005 Immunohistochemical analysis of MCT1, MCT2 and MCT4 expression in rat plantaris muscle. The Journal of physiology 80 15932892
2010 The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein. The Biochemical journal 79 20695846
2008 PGC-1alpha increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4. Physiological genomics 74 18523157
2013 MCT2 expression and lactate influx in anorexigenic and orexigenic neurons of the arcuate nucleus. PloS one 58 23638108
2007 Insulin and IGF-1 enhance the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin pathway. The European journal of neuroscience 52 18093179
2015 Localization of MCT2 at peroxisomes is associated with malignant transformation in prostate cancer. Journal of cellular and molecular medicine 50 25639644
2007 Noradrenaline enhances the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of PI3K/Akt and the mTOR/S6K pathway. Journal of neurochemistry 47 17394554
2011 Transport activity of the high-affinity monocarboxylate transporter MCT2 is enhanced by extracellular carbonic anhydrase IV but not by intracellular carbonic anhydrase II. The Journal of biological chemistry 45 21680735
2011 Brain-derived neurotrophic factor enhances the hippocampal expression of key postsynaptic proteins in vivo including the monocarboxylate transporter MCT2. Neuroscience 42 21736920
2003 Developmental and hormonal regulation of the monocarboxylate transporter 2 (MCT2) expression in the mouse germ cells. Biology of reproduction 42 12773420
2020 MCT2 overexpression rescues metabolic vulnerability and protects retinal ganglion cells in two models of glaucoma. Neurobiology of disease 41 32422282
2012 Monocarboxylate transporter 2 (MCT2) as putative biomarker in prostate cancer. The Prostate 41 23192371
2022 Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function. Proceedings of the National Academy of Sciences of the United States of America 40 35939682
2017 A neuronal MCT2 knockdown in the rat somatosensory cortex reduces both the NMR lactate signal and the BOLD response during whisker stimulation. PloS one 40 28388627
2003 Perinatal and early postnatal changes in the expression of monocarboxylate transporters MCT1 and MCT2 in the rat forebrain. The Journal of comparative neurology 39 12966567
2018 Curcumin Ameliorates Memory Deficits by Enhancing Lactate Content and MCT2 Expression in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease. Anatomical record (Hoboken, N.J. : 2007) 35 30312017
2012 Basigin interacts with both MCT1 and MCT2 in murine spermatozoa. Journal of cellular physiology 32 21792931
2009 Linking supply to demand: the neuronal monocarboxylate transporter MCT2 and the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid receptor GluR2/3 subunit are associated in a common trafficking process. The European journal of neuroscience 32 19453627
2015 Immunohistochemical localization of GLUT3, MCT1, and MCT2 in the testes of mice and rats: the use of different energy sources in spermatogenesis. Biomedical research (Tokyo, Japan) 30 26299481
2006 Expression of CD147 and monocarboxylate transporters MCT1, MCT2 and MCT4 in porcine small intestine and colon. Veterinary journal (London, England : 1997) 29 16901736
2005 Expression of MCT1, MCT2 and MCT4 in the rumen, small intestine and liver of reindeer (Rangifer tarandus tarandus L.). Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 29 15953554
2018 MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG. Nature chemical biology 26 30297875
2013 The neuroplastin adhesion molecules are accessory proteins that chaperone the monocarboxylate transporter MCT2 to the neuronal cell surface. PloS one 26 24260123
2015 Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer. Oncotarget 24 26035357
2003 Distribution of monocarboxylate transporter isoforms MCT1, MCT2 and MCT4 in porcine muscles. Acta physiologica Scandinavica 24 12492781
2008 Characterization and regulation of monocarboxylate cotransporters Slc16a7 and Slc16a3 in preimplantation mouse embryos. Biology of reproduction 23 18385447
2008 Distribution of the monocarboxylate transporter MCT2 in human cerebral cortex: an immunohistochemical study. Brain research 23 18598673
2023 Targeting the monocarboxylate transporter MCT2 and lactate dehydrogenase A LDHA in cancer cells with FX-11 and AR-C155858 inhibitors. European review for medical and pharmacological sciences 18 37522672
2009 Metabolic effects of blocking lactate transport in brain cortical tissue slices using an inhibitor specific to MCT1 and MCT2. Neurochemical research 18 19404741
2021 MCT2 overexpression promotes recovery of cognitive function by increasing mitochondrial biogenesis in a rat model of stroke. Animal cells and systems 16 34234890
2020 Prostate Cancer Proliferation Is Affected by the Subcellular Localization of MCT2 and Accompanied by Significant Peroxisomal Alterations. Cancers 15 33121137
2022 SLC16A7 Promotes Triglyceride Deposition by De Novo Lipogenesis in Chicken Muscle Tissue. Biology 13 36358250
2013 Expression and cellular localization of monocarboxylate transporters (MCT2, MCT7, and MCT8) along the cattle gastrointestinal tract. Cell and tissue research 13 23417128
2009 Regulation of the intracellular distribution, cell surface expression, and protein levels of AMPA receptor GluR2 subunits by the monocarboxylate transporter MCT2 in neuronal cells. Journal of neurochemistry 13 19457092
1997 Functional evidence for a monocarboxylate transporter (MCT) in strial marginal cells and molecular evidence for MCT1 and MCT2 in stria vascularis. Hearing research 13 9447934
2018 Neuroprotective effect of rLosac on supplement-deprived mouse cultured cortical neurons involves maintenance of monocarboxylate transporter MCT2 protein levels. Journal of neurochemistry 11 30347438
2014 The genetic variation in monocarboxylic acid transporter 2 (MCT2) has functional and clinical relevance with male infertility. Asian journal of andrology 11 24799634
2014 Glutamate reduces glucose utilization while concomitantly enhancing AQP9 and MCT2 expression in cultured rat hippocampal neurons. Frontiers in neuroscience 9 25161606
2010 Expression of lactate transporters MCT1, MCT2 and CD147 in the red blood cells of three horse breeds: Finnhorse, Standardbred and Thoroughbred. Equine veterinary journal. Supplement 7 21059000
2025 RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa. Proceedings of the National Academy of Sciences of the United States of America 4 40178895
2025 The interactions between monocarboxylate transporter genes MCT1, MCT2, and MCT4 and the kinetics of blood lactate production and removal after high-intensity efforts in elite males: a cross-sectional study. BMC genomics 3 39934699
2025 Knocking down the neuronal lactate transporter MCT2 in the arcuate nucleus of female rats increases food intake and body weight. Scientific reports 3 40032881
2025 Gastrodin alleviates mitochondrial energy metabolism dysfunction via activating β-catenin/c-Myc/MCT2 signaling in Alzheimer's disease models. Journal of ethnopharmacology 3 40915373
2025 Lactate Transport via Glial MCT1 and Neuronal MCT2 Is Not Required for Synchronized Synaptic Transmission in Hippocampal Slices Supplied With Glucose. Journal of neurochemistry 3 41048117
2025 Neuronal MCT2 promotes angiogenesis via lactate in the developing mouse neocortex. Cell death and differentiation 2 41046267
2024 Transcriptional expression of SLC16A7 as a biomarker of occult lymph node metastases in patients with head and neck squamous cell carcinoma. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 2 39215860
2022 MOG analogues to explore the MCT2 pharmacophore, α-ketoglutarate biology and cellular effects of N-oxalylglycine. Communications biology 2 36028752
2025 Associations Between Genetic Variants in MCT2 (rs3763980, rs995343, rs3763979) and MCT4 (rs11323780) with Blood Lactate Kinetics Before and After Supramaximal Exercise. International journal of molecular sciences 1 40869186
2019 [Acupuncture up-regulates MCT2 expression of peri-ischemic cortex in middle cerebral artery occlusion rats]. Zhen ci yan jiu = Acupuncture research 1 31368261
2026 Compensatory transporter upregulation facilitates retinal ganglion cell survival in glaucoma after MCT2 elimination. Frontiers in cell and developmental biology 0 42137367
2025 Tumor suppressing function of SLC16A7 in bladder cancer and its pan-cancer analysis. BMC cancer 0 40410718
2025 Acute restraint stress and epinephrine administration disrupt cognitive and emotional functions in male rats via modulation of proinflammatory cytokines, MCT-2, and neurogranin. Neuroscience letters 0 40930456

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