The DNAJC19 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human gastric adenocarcinoma cell line AGS. This product comprises a heterogeneous pool of cells carrying Cas9-mediated disruptions in the DNAJC19 gene, generating a loss-of-function model for studying mitochondrial co-chaperone biology and gastric cancer cell physiology.
The host AGS cell line is a well-established human gastric adenocarcinoma model derived from a 54-year-old female patient. AGS cells display epithelial morphology and serve as a versatile platform for studying oncogenic signaling, metabolic reprogramming, and chemotherapeutic response in gastric cancer. Their widespread use in cancer biology makes them an ideal background for interrogating mitochondrial contributions to tumorigenesis.
DNAJC19 encodes a mitochondrial inner membrane J-domain co-chaperone that cooperates with mtHsp70 (HSPA9) to drive ATP-dependent import of nuclear-encoded precursor proteins through the TIM23 translocase complex. The protein directly interacts with TIM44, PAM16, TIMM23, and TIMM17A, facilitating precursor handoff and processing by the mitochondrial processing peptidase (MPP). DNAJC19 activity is transcriptionally regulated by PGC-1??, NRF1, and TFAM, and its function is modulated by mitochondrial membrane potential and ROS levels. Downstream consequences of DNAJC19 knockout include impaired assembly of oxidative phosphorylation complexes containing subunits such as ATP5A and SDHA, altered HSP60 levels, and increased cytochrome c release leading to apoptotic signaling.
In AGS gastric adenocarcinoma cells, DNAJC19 disruption perturbs mitochondrial proteostasis and bioenergetics, making this knockout model particularly relevant for dissecting the interplay between mitochondrial function and gastric cancer progression. Given the reliance of cancer cells on mitochondrial metabolism and the UPRmt stress response, loss of DNAJC19 may sensitize cells to metabolic inhibitors or chemotherapeutic agents, providing a platform to investigate synthetic lethal interactions and adaptive mechanisms. This model also enables exploration of how mitochondrial dysfunction influences epithelial-to-mesenchymal transition and metastatic behavior in a gastric cancer context.
Researchers can utilize this polyclonal knockout pool to examine DNAJC19-dependent mitochondrial protein import defects via Western blotting of TIM23 complex members or Seahorse respirometry for oxidative phosphorylation capacity (OCR) and glycolytic flux (ECAR). Immunofluorescence microscopy enables assessment of mitochondrial morphology, while co-immunoprecipitation assays reveal altered interactions between HSPA9, TIM44, and other translocase components. The model supports viability and apoptosis studies under drug challenge (e.g., cisplatin) and migration/invasion assays to evaluate metastatic potential. RNA analyses via RT-qPCR can probe transcriptional responses of mitochondrial genes, linking DNAJC19 loss to broader stress signaling outputs. For further technical information or custom gene editing solutions, please contact Ascent Research.
