| 2019 |
Aurora-A kinase directly interacts with and phosphorylates LDHB at serine 162, which increases LDHB activity in reducing pyruvate to lactate. Mechanistically, S162 phosphorylation relieves substrate inhibition by pyruvate, resulting in elevated conversion of pyruvate and NADH to lactate and NAD+, thereby promoting glycolytic flux and the Warburg effect. Expression of LDHB-S162A mutant blocked glycolysis and tumor growth. |
Co-IP, in vitro kinase assay, site-directed mutagenesis (S162A), xenograft tumor models, metabolic flux measurements |
Nature communications |
High |
31804482
|
| 2018 |
SIRT5 binds LDHB and deacetylates it at lysine-329, thereby promoting LDHB enzymatic activity. Deacetylated LDHB increases autophagy and colorectal cancer cell growth. SIRT5 knockout or inhibition increased LDHB acetylation at K329 and inhibited LDHB activity, downregulating autophagy and cancer cell growth. |
Mass spectrometry identification of SIRT5 as binding partner, Co-IP, SIRT5 knockout/inhibition, enzymatic activity assays, in vitro and in vivo tumor growth assays |
Molecular oncology |
High |
30443978
|
| 2021 |
R-2-hydroxyglutarate (R-2HG) suppresses aerobic glycolysis in leukemia by abrogating FTO/m6A/YTHDF2-mediated post-transcriptional upregulation of LDHB expression. Knockdown of LDHB recapitulates R-2HG-induced glycolytic inhibition, and LDHB overexpression reverses the R-2HG effect, placing LDHB downstream of the FTO/m6A axis in glycolytic regulation. |
shRNA knockdown, overexpression rescue experiments, m6A modification analysis, in vivo leukemogenesis model |
Molecular cell |
High |
33434505
|
| 2024 |
HMOX1 interacts with LDHB in foamy macrophages during advanced atherosclerosis. This HMOX1-LDHB interaction enables LONP1 to degrade mitochondrial transcription factor TFAM, leading to mitochondrial dysfunction and ferroptosis. |
Bulk and single-cell RNA sequencing, protein interaction studies, LONP1 inhibitor experiments, MitoTEMPO treatment in vivo |
Developmental cell |
Medium |
39731912
|
| 2024 |
LDHB inhibition in lung cancer cells decreases total intracellular glutathione (GSH) levels, specifically reducing mitochondrial GSH catabolism by gamma-L-Glutamyl transpeptidase (GGT). GSH-monoethyl ester supplementation partially rescued the reduced invasion, migration, and colony formation caused by LDHB silencing, establishing that LDHB supports metastatic potential through mitochondrial GSH catabolism. |
siRNA silencing, metabolic inhibitor experiments, GSH supplementation rescue, in vivo metastasis models in immunodeficient and immunocompetent mice |
Cancer letters |
Medium |
39615645
|
| 2024 |
LDHB interacts with vacuolar-type proton ATPase catalytic subunit A (ATP6V1A), promoting lysosomal acidification and autophagic flux. The residues leucine 57 in ATP6V1A and serine 269 in LDHB are critical for their interaction. Hydrogen sulfide (H2S) donor NaHS attenuates disturbed flow-induced vascular remodeling by inhibiting LDHB and disrupting the LDHB-ATP6V1A interaction. |
RNA-Seq, Co-IP, mutagenesis of interaction residues (Leu57, Ser269), LDHB overexpression rescue, in vivo vascular remodeling model |
Redox biology |
Medium |
39647238
|
| 2024 |
LDHB has β cell-specific expression in human islets and limits lactate generation. LDHB inhibition amplifies LDHA-dependent lactate generation and increases basal insulin release in both mouse and human β cells. Mendelian randomization shows that low LDHB expression correlates with elevated fasting insulin. |
13C6 glucose labeling with GC-MS and 2D NMR metabolic mapping, LDHB inhibition in islets, Mendelian randomization |
Cell reports |
High |
38607916
|
| 2024 |
STAT3 transcription factor binds the promoter region of LDHB and activates its transcription in endometrial cancer cells. LDHB in turn interacts with and upregulates MDH2 expression, promoting cancer cell malignancy. |
ChIP assay, dual-luciferase reporter assay, Co-IP, LDHB and STAT3 knockdown with phenotypic rescue by MDH2 overexpression |
Molecular biotechnology |
Medium |
38381377
|
| 2024 |
LDHB modulates lactate production and histone H3K18 lactylation at the PD-L1 promoter to promote PD-L1 expression and immune evasion in ovarian cancer. LDHB knockdown reduced H3K18 lactylation at the PD-L1 promoter and decreased PD-L1 expression, enhancing T cell killing. |
ChIP-qPCR, luciferase reporter assay, LDHB siRNA knockdown, T cell co-culture cytotoxicity assay, ELISA for immune factors |
Cancer investigation |
Medium |
39587817
|
| 2024 |
SARS-CoV-2 Spike S1 domain interacts with LDHB and inhibits its catalytic activity, leading to increased lactate levels and a metabolic switch from aerobic to anaerobic metabolism. The Spike-NAD+ interacting region mainly involves W436 within the RBD domain, suggesting Spike deprives LDHB of NAD+. |
AP-MS interactome, Co-IP, immunofluorescence colocalization, enzymatic activity assay in HEK-293T cells overexpressing S1 |
International journal of biological macromolecules |
Medium |
39147351
|
| 2024 |
PGC-1α transcriptionally upregulates LDHB synthesis; PGC-1α overexpression increases LDHB expression, reduces protein lactylation, and induces a switch from lactate to pyruvate production in APAP-induced liver injury model. |
Lentiviral overexpression of SIRT1 and PGC-1α, Western blot, measurement of lactylation and mitochondrial damage markers in AML12 cells and C57/BL6 mice |
Pharmacological research |
Medium |
38810904
|
| 2024 |
LDHB silencing in lung cancer cells decreases nucleotide metabolism (purine and pyrimidine biosynthesis) as shown by metabolomics of tumor xenografts, impairs DNA damage repair, and sensitizes cells to radiotherapy. Nucleotide supplementation partially rescued DNA damage caused by combined LDHB silencing and radiotherapy. |
Transcriptomic re-analysis, γH2AX immunofluorescence, cell cycle analysis, metabolomics of xenografts, nucleotide supplementation rescue |
Scientific reports |
Medium |
40158058
|
| 2025 |
In SLE neutrophils, chronic TLR7/9 signaling represses mitochondrial LDHB expression, impairing lactate sensing and suicidal NETosis; neutrophils instead default to vital NET release. Restoring LDHB expression (via HCQ + IFNAR blockade) re-establishes suicidal NETosis and bacterial clearance. |
Lupus-prone mouse model, LDHB expression analysis, HCQ and anifrolumab treatment in SLE patient neutrophils, NETosis assays |
bioRxivpreprint |
Medium |
41279671
|
| 2026 |
LDHB deficiency in cancer-associated fibroblasts (CAFs) leads to lactate accumulation, which disrupts DUSP16-p38 interaction, causing sustained p38 activation. This reprograms CAFs into an inflammatory phenotype with CXCL8 secretion that enhances breast cancer metastasis. |
LDHB knockout in CAFs, Co-IP for DUSP16-p38 interaction, CXCL8 secretion assay, in vivo metastasis model |
Cancer research |
Medium |
41686427
|
| 2026 |
UCHL1 deubiquitinase binds LDHB and deubiquitinates it, thereby stabilizing LDHB protein and promoting osteosarcoma progression. LDHB knockdown reversed UCHL1-driven oncogenesis. |
Co-immunoprecipitation, ubiquitination assay, shRNA knockdown of UCHL1 and LDHB, xenograft model |
Discover oncology |
Medium |
41998400
|
| 2026 |
LDHB K156 lactylation, regulated by the EP300/HDAC2 axis, is induced downstream of cGAS-STING-mediated glycolytic reprogramming in sepsis, amplifying NLRP3 inflammasome activation and renal injury. AAV-mediated expression of K156R lactylation-deficient LDHB reduced renal dysfunction compared to wild-type LDHB. |
Lactyl-proteomic screening, CLP mouse model, AAV-mediated tubule-specific expression of WT vs K156R LDHB, biochemical assays for EP300/HDAC2 regulation |
Life sciences |
Medium |
41796892
|
| 2026 |
In blood-brain barrier endothelial cells, extracellular lactate upregulates LDHB, MPC1, MPC2, and PDH, driving lactate-derived pyruvate into mitochondria and fueling TCA cycle and oxidative phosphorylation. Genetic silencing of LDHB abolishes lactate-driven BEC proliferation, establishing LDHB as the entry point of an LDHB-MPC-NAD+ redox-metabolic axis. |
LDHB siRNA silencing, high-resolution respirometry, MPC1 inhibition, NAMPT inhibition, glucose uptake and GLUT1 measurements |
Free radical biology & medicine |
Medium |
42217683
|
| 2025 |
In Schwann cells (peripheral nerve glia), LDHB is required for motor function: SC-specific LDHB deletion caused robust motor defects, whereas motor neuron-specific deletion had little effect. In addition, Ldhb knockout mice develop progressive neuromuscular junction atrophy. Motor-neuron LDHB deficiency synergizes with ALS risk variants (TDP43-Q331K, Sod1-D83G) to produce early motor neuropathy. |
Cell-type-specific conditional LDHB knockout (Schwann cell vs motor neuron), neuromuscular junction histology, motor behavior assays, ALS knock-in allele genetic epistasis |
bioRxivpreprint |
Medium |
bio_10.1101_2025.11.24.690227
|
| 2026 |
YBX1 promotes LDHB expression by increasing LDHB transcriptional activity and stabilizing LDHB mRNA. Elevated LDHB drives conversion of lactate to pyruvate and then acetyl-CoA, enhancing TCA cycle activity and ATP production in intrahepatic cholangiocarcinoma cells. Lactate induces YBX1 nuclear translocation, which activates LDHB transcription in a feed-forward loop. |
YBX1 overexpression/knockout (CRISPR-Cas9), LDHB knockout, mRNA stability assays, metabolic flux measurements (TCA cycle activity, ATP), in vitro and in vivo tumor growth |
Pharmacological research |
Medium |
41577157
|
| 1996 |
A naturally occurring LDHB variant (LDHB GUA1) carries an Arg-to-Trp substitution at residue 106 in the active site loop. This Arg106 residue is conserved across evolution and resides in the hinge of a loop that closes over the active site upon substrate binding; the substitution abolishes catalytic activity by preventing polarization of the substrate carbonyl bond, while maintaining normal kinetic properties in heterotetramers with active LDHA subunits. |
DNA sequencing identifying C→T transition (Arg106Trp), computer modeling using published crystal structures, kinetic analysis of heterotetramers |
Biochimica et biophysica acta |
Medium |
8611651
|
| 2020 |
LDHB interacts with CSFV non-structural protein NS3. LDHB knockdown induces mitochondrial fission and mitophagy (evidenced by decreased TOMM20 and VDAC1, and promoted ubiquitination of MFN2) and promotes NFKB signaling, creating conditions conducive to viral persistence. LDHB overexpression decreased CSFV replication. |
Yeast two-hybrid screening, Co-IP, GST pulldown, confocal colocalization, siRNA knockdown, dual fluorescence mitophagy reporter (mito-mRFP-EGFP), viral titer assays |
Autophagy |
Medium |
32924761
|
| 2024 |
FGF1/2 signaling positively regulates STAT1, which transcriptionally activates LDHA expression while suppressing LDHB expression in prostate cancer cells, thereby promoting glycolysis. |
RT-qPCR, Western blot, ECAR glycolysis measurements, FGF pathway inhibitor in xenograft model, STAT1 knockdown/overexpression |
Journal of translational medicine |
Medium |
38764020
|
| 2026 |
Maternal LDHB is required for NAD+/NADH redox homeostasis during the 4- to 8-cell transition in preimplantation embryo development. Inhibition of LDHB caused developmental arrest, reduced ATP, impaired mitochondrial function, and decreased NAD+/NADH ratio. Aspartate supplementation rescued developmental progression via the malate-aspartate shuttle. |
Transient pharmacological inhibition of LDHB in early mouse embryos, metabolic readouts (ATP, NAD+/NADH), aspartate supplementation rescue, mitochondrial function assays |
FASEB journal |
Medium |
42117986
|
| 2025 |
LDHB silencing in pleural mesothelioma cells increases nuclear DNA damage (elevated γH2AX) by impairing nucleotide synthesis, which is reversed by nucleotide supplementation. LDHB inhibition reduced tumor growth in vivo and enhanced cisplatin efficacy. |
siRNA and inducible shRNA silencing, γH2AX measurement, nucleotide supplementation rescue, in vivo xenograft with cisplatin combination |
Oncogenesis |
Medium |
40790017
|
| 2015 |
LDHB promoter hypermethylation suppresses LDHB expression in pancreatic cancer, leading to glycolytic transition. Decreased LDHB expression promotes proliferation, invasion, and migration in hypoxia, establishing LDHB as a suppressor of glycolysis in this context. |
Promoter methylation analysis, LDHB knockdown/overexpression, functional assays (proliferation, invasion, migration), glycolysis measurements |
Medical oncology |
Medium |
25807933
|
| 2022 |
LDHB overexpression in CD4 T cells increases cell respiration and mitigates lactic acid-induced inhibition of intracellular cytokine production. LDHB-overexpressing T cells preferentially migrated into HCT116 tumor spheroids and displayed higher expression of cytotoxic effector molecules. |
LDHB overexpression in human CD4 T cells, Seahorse metabolic assay, tumor spheroid migration assay, flow cytometry for cytokine and effector molecule expression |
International journal of molecular sciences |
Medium |
35682650
|
| 2025 |
Mechanical stress activates IER3, which upregulates LDHB (identified as downstream target by mass spectrometry). LDHB promotes lactate production and lactylation in BMSCs, which drives osteogenic differentiation. IER3 inhibition blocked mechanical stress-induced increases in lactate and lactylation. |
Mass spectrometry identification of LDHB as IER3 target, uniaxial cell stretching system, IER3 knockdown with lactylation and differentiation assays |
FASEB journal |
Low |
40244862
|
| 2025 |
Visomitin directly targets STAT3, inhibiting its transcriptional activity and thereby modulating LDHB expression levels in osteoclasts, triggering metabolic reprogramming and reducing osteoclastogenesis. |
STAT3 targeting assay, LDHB expression analysis, osteoclastogenesis assays, in vivo bone loss model |
Research (Washington, D.C.) |
Low |
40698330
|
| 2025 |
Luteolin and quercetin exhibit uncompetitive inhibition of LDHB by binding at an allosteric site at the dimer interface, distinct from the active site where they competitively inhibit LDHA. This was supported by enzyme kinetic assays and molecular docking. |
In vitro enzyme kinetic assays (Ki determination, inhibition mode), molecular docking, virtual screening of 115 compounds |
Molecules (Basel, Switzerland) |
Low |
40733189
|
| 2021 |
HYOU1 promotes LDHB expression at the post-transcriptional level by stabilizing LDHB mRNA through suppression of miR-375-3p levels. LDHB overexpression rescued the inhibitory effects of HYOU1 silencing on glycolysis, proliferation, and invasion in papillary thyroid cancer cells. |
HYOU1 siRNA silencing, miR-375-3p measurement, 3'UTR targeting analysis, LDHB overexpression rescue of glycolysis and proliferation |
Journal of cellular and molecular medicine |
Low |
33792181
|
| 2025 |
LDHB directly interacts with PDCoV nucleocapsid (N) protein in the cytoplasm and mediates autophagic degradation of the N protein, thereby suppressing viral replication. PDCoV N protein, via its LIR motif, binds LC3 and facilitates LDHB degradation as a viral immune evasion strategy. |
Co-IP, yeast two-hybrid, confocal colocalization, siRNA knockdown, LDHB overexpression, viral titer assays, autophagy flux assays |
Microbiology spectrum |
Medium |
40231829
|