Ask about this productRelated genes to: DLAT antibody
- Gene:
- DLAT NIH gene
- Name:
- dihydrolipoamide S-acetyltransferase
- Previous symbol:
- DLTA
- Synonyms:
- PDC-E2, E2
- Chromosome:
- 11q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 1989-06-30
- Date modifiied:
- 2018-12-14
Related products to: DLAT antibody
Related articles to: DLAT antibody
- Metabolic reprogramming is a hallmark of cancer and requires coordinated regulation of glycolysis and mitochondrial metabolism. The pyruvate dehydrogenase complex (PDC) links these pathways by catalyzing the conversion of pyruvate to acetyl-CoA, yet the epigenetic mechanisms regulating PDC expression remain poorly understood. We investigated whether the histone demethylase KDM4B regulates PDC expression and mitochondrial metabolism in cancer cells. Human colorectal carcinoma (HCT-116), cervical adenocarcinoma (HeLa), melanoma (G-361), and non-malignant human proximal tubule epithelial (HK-2) cells were analyzed using glucose-response assays, RNA sequencing, RT-qPCR, immunoblotting, metabolic assays, fluorescence imaging, and cell viability analyses. KDM4B was disrupted by small interfering RNA (siRNA) and the selective inhibitor NCGC00244536. Glucose availability induced coordinated upregulation of the PDC subunits PDHA1, DLD, and DLAT and was associated with increased proliferation and KDM4B expression in cancer cells. Both genetic depletion and pharmacological inhibition of KDM4B suppressed PDC expression and increased the repressive histone mark H3K9me3. Exploratory RNA-seq analysis revealed coordinated metabolic transcriptional reprogramming characterized by induction of glycolytic genes and suppression of PDC, the tricarboxylic acid cycle, and electron transport chain genes, together with increased PDK1 and reduced PDP1 expression, consistent with impaired mitochondrial glucose oxidation. These changes were accompanied by reduced pyruvate dehydrogenase activity, extracellular pyruvate accumulation, ATP depletion, impaired glucose uptake, mitochondrial depolarization, caspase-3 activation, increased lactate dehydrogenase release, reduced viability, and diminished proliferative capacity. These effects were generally more pronounced in the cancer cell models than in HK-2 cells. Our findings identify KDM4B as a regulator associated with maintenance of PDC expression and mitochondrial glucose metabolism in cancer cells. KDM4B inhibition suppresses PDC abundance and activity and is accompanied by metabolic dysfunction, mitochondrial depolarization, and reduced cell survival. These findings support a model in which the KDM4B-PDC axis may contribute to metabolic homeostasis and survival in cancer cells and suggest that this pathway may represent a potential therapeutic vulnerability. - Source: PubMed
Publication date: 2026/09/16
Sato SachikoHasan Arif UlObara MamiTaira Eiichi - Preeclampsia (PE) is characterized by placental hypoxia, metabolic stress, trophoblast dysfunction, and impaired spiral artery remodeling, but the mechanisms linking these abnormalities remain incompletely understood. Cuproptosis, a recently identified form of regulated cell death driven by copper-dependent aggregation of lipoylated tricarboxylic acid cycle proteins, may provide a mechanistic link between placental metabolic stress and trophoblast injury. Here, we propose a hypothesis in which hypoxia-induced glycolytic reprogramming and lactate accumulation promote histone H3K18 lactylation, activate GRHL2, and increase SLC31A1/CTR1-mediated copper uptake. Subsequent FDX1-dependent copper reduction, DLAT aggregation, Fe-S cluster loss, and mitochondrial proteotoxic stress may preferentially affect mitochondria-rich villous syncytiotrophoblasts, while also impairing EVT function. Cuproptosis may interact with ferroptosis and oxidative stress through shared metal-redox and mitochondrial vulnerabilities. Although current evidence does not establish cuproptosis as an initiating cause of PE, it may amplify placental dysfunction. Targeting copper transport, mitochondrial stress, or pathway-specific biomarkers warrants further investigation. - Source: PubMed
Publication date: 2026/09/09
Liu LingXing BaoxiangZhang Yan - To observe the effects of electroacupuncture (EA) intervention at different time points on cuproptosis-related proteins and Cu levels in the ischemic penumbra of rats with cerebral ischemia-reperfusion injury (CIRI) after acute ischemic stroke (IS), so as to explore the mechanism by which acupuncture inhibits cuproptosis to improve neurological function in CIRI rats, as well as the therapeutic efficacy of intervention administered at different time windows. - Source: PubMed
Wang YufeiMeng JiaHuang Liujiao - To explore the mechanism by which moxibustion with seed-sized moxa cones improves colonic tissue damage by regulating the cuproptosis signaling pathway in mice with ulcerative colitis (UC). - Source: PubMed
Cui YaohuiChang BoyaXu HuichaoWang HaijunJi Laixi - Traumatic brain injury (TBI) is a leading cause of disability and mortality, with secondary injury mechanisms involving neuronal death and neuroinflammation, for which effective treatments remain limited. Neutrophil extracellular traps (NETs) are implicated in post-TBI neuropathology. Cuproptosis, a copper-dependent cell death pathway characterized by mitochondrial oxidative stress, dysfunction, and disrupted dynamics, has recently been implicated in neurological disorders. This study aims to investigate whether NETs exacerbate secondary brain injury by promoting neuronal cuproptosis after TBI and to elucidate the underlying molecular mechanism. We observed elevated NET levels in brain tissues from both TBI patients and mice, which correlated with poor prognosis. Single-cell RNA sequencing revealed a significant upregulation of transthyretin (Ttr) in neurons post-TBI. Mechanistically, NETs deliver lactylated S100a9 (S100a9K26la), a glycolysis-dependent lactylated protein, to neurons. S100a9K26la translocates to the nucleus and promotes Ttr transcription. Increased neuronal Ttr protein then competes with ATPase copper transporting β (Atp7b) for binding to copper metabolism MURR1 domain-containing 1 (Commd1) at the W123 residue. This competition disrupts the Commd1-Atp7b interaction, impairing copper efflux and leading to intracellular copper accumulation, mitochondrial oxidative stress, aggregation of DLAT, loss of Fe-S cluster proteins, and ultimately neuronal cuproptosis. Neuron-specific Ttr conditional knockout ameliorated neuronal death, neuroinflammation, blood-brain barrier (BBB) disruption, and neurological deficits in a TBI model. Conversely, inhibition of cuproptosis with the copper chelator tetrathiomolybdate (TTM) yielded similar protective effects. In summary, our findings elucidate a novel pathway wherein NETs, via delivery of S100a9K26la, drive neuronal Ttr overexpression. Ttr disrupts copper homeostasis by interfering with the Commd1-Atp7b axis, ultimately triggering neuronal cuproptosis and exacerbating secondary injury after TBI. This study identifies NETosis and the Ttr/Commd1/Atp7b axis as potential therapeutic targets for mitigating TBI-induced damage. - Source: PubMed
Publication date: 2026/09/21
Xu JianyeZhang XuLiu YangChen BoZhang YaoWang JinchaoCao YiyaoLi ShenghuiWu RuojieSun DongdongLi LeiLiu XiaoYang GuiliWang ZengguangGuo XingLi WeiguoZhang Shu