The LYRM9 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-mediated polyclonal knockout cell population designed to disrupt the LYRM9 gene in the human AGS gastric adenocarcinoma cell line. This pooled product provides a loss-of-function model comprising a diverse array of editing events, enabling functional studies of LYRM9 in a genetically heterogeneous context that more closely recapitulates tumor cellular heterogeneity compared to clonal lines.
The AGS host cell line is an adherent epithelial line derived from a patient with gastric adenocarcinoma. It is widely employed as a model for gastric epithelial biology, including investigations of cancer signaling, proliferation, and metabolic adaptation, and it retains characteristics of the original tumor, making it a relevant system for gastric cancer research.
LYRM9 encodes a mitochondrial protein critical for iron-sulfur (Fe-S) cluster assembly, a process required for the stability and function of numerous proteins, including those of the electron transport chain (ETC). LYRM9 interacts with core Fe-S cluster machinery components such as ISCU, NFS1, FXN, and GLRX5 to facilitate the maturation of apoproteins, prominently the respiratory complex subunits NDUFS1 (Complex I), SDHB (Complex II), and UQCRC2 (Complex III). Consequently, LYRM9 is essential for maintaining oxidative phosphorylation (OXPHOS) and cellular iron homeostasis. The expression of LYRM9 is transcriptionally regulated by upstream factors including NRF1, NRF2, PGC-1??, and iron regulatory proteins, linking mitochondrial biogenesis and metabolic cues to Fe-S cluster biogenesis. Disruption of LYRM9 impairs electron carrier assembly, leading to compromised respiratory complex activity and potential metabolic rewiring.
In AGS gastric adenocarcinoma cells, LYRM9 knockout serves as a powerful tool to dissect the role of mitochondrial metabolism in cancer. Loss of Fe-S cluster integrity disrupts OXPHOS, likely forcing cells to rely on glycolysis, and thus provides a model to study metabolic plasticity and vulnerabilities in gastric cancer. This system is also pertinent to investigations of mitochondrial dysfunction syndromes and iron-sulfur cluster deficiency states.
This polyclonal knockout cell product is suitable for a range of assays, including Western blotting to assess steady-state levels of respiratory complex subunits, Blue Native PAGE to evaluate supercomplex assembly, oxygen consumption rate (OCR) analysis to quantify mitochondrial respiration, aconitase activity measurements for Fe-S cluster integrity, RT-qPCR profiling of nuclear- and mitochondrial-encoded ETC genes, and cell viability assays in glucose- versus galactose-containing media to probe OXPHOS dependence. These applications support research in mitochondrial biology, cancer metabolism, and functional genomics. For additional details, please contact Ascent Research.
