The DLAT Knockout NCI-H1299 Polyclonal Cells product consists of a polyclonal population of NCI-H1299 cells with CRISPR/Cas9-mediated disruption of the DLAT gene, generating a heterogeneous loss-of-function model. This knockout cell pool enables investigation of DLAT-dependent mitochondrial biology without the selective pressures of clonal isolation, preserving the varied metabolic phenotypes inherent to polyclonal populations.
NCI-H1299 is a human non-small cell lung cancer (NSCLC) cell line derived from a lymph node metastasis of lung adenocarcinoma. These epithelial cells are widely employed to model metastatic disease and oncogenic metabolic reprogramming, particularly the Warburg effect, and serve as a clinically relevant platform for assessing metabolic vulnerabilities in aggressive lung tumors.
DLAT encodes the dihydrolipoamide acetyltransferase (E2) subunit of the mitochondrial pyruvate dehydrogenase complex (PDC), which catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA, a critical step linking glycolysis to the tricarboxylic acid cycle. The E2 subunit forms the structural core of the PDC and interacts with E1 (PDHA1/PDHB), E3 (DLD), and the E3-binding protein (PDHX). PDC activity is tightly controlled by reversible phosphorylation: pyruvate dehydrogenase kinase 1 (PDK1) inactivates the complex, whereas pyruvate dehydrogenase phosphatase 1 (PDP1) reactivates it, processes modulated by insulin signaling and nutrient availability. Acetyl-CoA produced by DLAT fuels the TCA cycle, fatty acid biosynthesis, and histone acetylation, positioning DLAT as a central regulator of cellular energetics and epigenetic programs.
In the NCI-H1299 context, DLAT knockout disrupts mitochondrial pyruvate oxidation, forcing cells to rely on alternative pathways such as glycolysis and glutaminolysis. This metabolic blockade models features of pyruvate dehydrogenase deficiency and cancer metabolic reprogramming. The polyclonal nature captures heterogeneous adaptive responses, enabling studies of how NSCLC cells compensate for PDC dysfunction. As NCI-H1299 cells exhibit a highly glycolytic phenotype, DLAT loss may deepen the Warburg effect, revealing metabolic susceptibilities for therapeutic exploration.
This product is suited for cancer metabolism research, Warburg effect analysis, and drug target validation. Representative assays include metabolic flux analysis, Seahorse respirometry, Western blot, RT-qPCR, immunofluorescence, and functional assays for apoptosis, proliferation, and drug sensitivity. The polyclonal DLAT knockout model offers a robust tool for dissecting mitochondrial dysfunction and metabolic adaptation in lung adenocarcinoma. For further details, please contact Ascent Research.
