Ask about this productRelated genes to: DLAT Blocking Peptide
- 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 Blocking Peptide
Related articles to: DLAT Blocking Peptide
- To investigate the molecular mechanism by which Formula (HJF) and its active component ursolic acid inhibit colorectal cancer (CRC) cell growth. - Source: PubMed
Jin ChenghuanHong ZongchaoDuan XueyunFan HengYang JingxingQin JiameiZou LiyanQin Mengyuan - Myocardial ischemia remains a leading cause of mortality worldwide, yet the molecular mechanisms underlying ischemia-induced cardiomyocyte death are incompletely understood. Here, we investigated whether nucleophosmin 1 (NPM1) regulates cuproptosis, a newly identified form of copper-dependent cell death, in the setting of ischemic injury. Using a CoCl-induced H9C2 cardiomyocyte ischemia model, we found that CoCl triggered hallmark features of cuproptosis, including loss of Fe-S cluster proteins (FDX1, DLAT, and DLST), reduced lipoylation of DLAT and DLST, and enhanced DLAT oligomerization, accompanied by impaired cell viability, all of which were reversed by the cuproptosis inhibitor TTM. ES-Cu, a copper ionophore, similarly induced dose-dependent cuproptosis and cytotoxicity. Protein-protein interaction analysis suggested associations between NPM1 and key regulators of cuproptosis. Functionally, siRNA-mediated NPM1 knockdown attenuated CoCl-induced cuproptotic alterations and rescued cell viability, whereas NPM1 overexpression exacerbated these effects. Collectively, these loss- and gain-of-function studies establish NPM1 as a positive regulator of cuproptosis in myocardial ischemia. Our findings uncover a previously unrecognized role for NPM1 in mediating ischemic cardiomyocyte death via the cuproptosis pathway and highlight the NPM1-cuproptosis axis as a potential therapeutic target for ischemic heart disease. - Source: PubMed
Publication date: 2026/04/21
Su Yi-FanZhang Gao-Feng - Mitochondria-lysosome contacts regulates metabolic reprogramming in cancer, yet its role in glioblastoma pathogenesis remains poorly defined. - Source: PubMed
Publication date: 2026/04/21
Huang YanpingSu DongyuanCui XiaotengDing YaqingZhan QiHong BiaoZhao JixingXu HanyiCui LongtaoCheng ChunchaoJu JiashengWang QixueWang YunfeiYang EryanYi KaikaiPeng DazhaoHu HuiminKang Chunsheng - Excessive advanced glycation end products (AGEs) can lead to cardiovascular diseases such as myocardial fibrosis (MF). Although studies have found that AGEs induce cuproptosis, and cuproptosis promotes fibrosis, it has not been confirmed whether AGEs promote MF through cuproptosis. AGEs increased intracellular copper levels, promoted the expression of solute carrier family 31 member 1 (SLC31A1), and downregulated the expression of ferredoxin 1 (FDX1), lipoic acid synthetase (LIAS), lipoylated (Lip)-dihydrolipoamide S-succinyltransferase (DLST), and Lip-dihydrolipoamide S-acetyltransferase (DLAT) in cardiac fibroblasts (CFs). All of these key cuproptosis regulatory gene expression abnormalities indicate that cuproptosis is induced. AGEs also decreased adenosine triphosphate content and inhibited the activities of mitochondrial complexes I and III, but these regulatory effects were significantly weakened after SLC31A1 downregulation. Meanwhile, AGEs significantly promoted the expression of alpha smooth muscle actin, collagen I, collagen III, and transforming growth factor-β1, while SLC31A1 siRNA or copper chelator ammonium tetrathiomolybdate (TTM) blocked these promoting effects. Similarly, CuCl also induced fibrosis gene expression, while SLC31A1 overexpression (SLC31A1-O) further enhanced these effects, but TTM reduced CF activation induced by CuCl plus SLC31A1-O. In addition, AGEs significantly promoted cell migration and enhanced the expression and secretion of matrix metalloproteinase (MMP)-2 and MMP-9, while SLC31A1 siRNA or TTM weakened these effects. SLC31A1-O plus copper treatment also had similar effects to AGEs, and these effects could also be blocked by TTM. Therefore, AGEs enhance copper transport by promoting SLC31A1 expression, which leads to intracellular copper overload and then induces cuproptosis, and finally promotes CF activation and migration. - Source: PubMed
Publication date: 2026/04/20
Xiao JianShi Zan-HuaMa Xin-HuaXu Dao-MiaoMing Guang-Feng - Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with limited therapeutic options for advanced-stage patients. Here, we identify DLAT, a key enzyme in mitochondrial metabolism, as a critical driver of CRC progression. Multi-omics analyses revealed that DLAT was overexpressed in CRC tissues and correlated with poor patient prognosis. The results showed that DLAT promoted CRC growth by promoting the resistance to mitochondrial antioxidant stress and suppressing ferroptosis. Mechanistically, DLAT directly bond to the mitochondrial glutathione (mtGSH) transporter SLC25A39 and enhanced its protein stability independent of intracellular GSH levels, leading to the maintain of mitochondrial GSH (mtGSH) import and redox homeostasis. Knockdown of DLAT or SLC25A39 disrupted mtGSH transport, elevated lipid peroxidation, and sensitized CRC cells to ferroptosis. We further identified a small molecular drug GL-V9 as a DLAT degrader. GL-V9 bond to DLAT and induced DLAT degradation through ubiquitin-proteasome pathway. The disruption of DLAT-SLC25A39 axis by GL-V9 led to mtGSH depletion and oxidative stress, as well as the significant suppression of CRC growth. These findings establish DLAT as a metabolic vulnerability in CRC and highlight GL-V9 as a promising therapeutic agent. - Source: PubMed
Publication date: 2026/04/18
Zhang KunZhang XinHuang ChenqiYang JunyiDong LongxuanChen XijingXun ChenGuo Yongjian