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Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...

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Related Experiment Video

Updated: Jun 12, 2026

Use of a Hanging-weight System for Liver Ischemia in Mice
05:53

Use of a Hanging-weight System for Liver Ischemia in Mice

Published on: August 7, 2012

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DRP1 depletion protects NK cells from hypoxia-induced dysfunction.

Tias Verhezen1, Astrid Van Den Eynde1, Peter Verstraelen2

  • 1Center for Oncological Research (CORE), Integrated Precision and Personalized Oncology Network (IPPON), University of Antwerp, Antwerpen, Belgium.

Redox Report : Communications in Free Radical Research
|February 18, 2026
PubMed
Summary

Hypoxia impairs natural killer (NK) cell function in solid tumors. Inactivating DRP1 protein restores NK cell mitochondria and cytotoxic activity in hypoxic conditions, enhancing CAR-NK cell efficacy.

Keywords:
CRISPR-Cas9CancerDRP1HypoxiaMitochondriaNatural killer cellsROSTumor microenvironment

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Related Experiment Videos

Last Updated: Jun 12, 2026

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Dextran Enhances the Lentiviral Transduction Efficiency of Murine and Human Primary NK Cells
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Analysis of Human Natural Killer Cell Metabolism
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Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • Cellular therapies show limited efficacy in solid tumors, largely due to the immunosuppressive tumor microenvironment.
  • Tumor hypoxia significantly impairs natural killer (NK) cell function, a critical component of innate immunity against cancer.

Purpose of the Study:

  • To investigate the impact of hypoxia on NK cell function.
  • To evaluate strategies for restoring NK cell activity under hypoxic conditions.

Main Methods:

  • NK cells (unarmed or CAR-engineered) were cultured in normoxia or hypoxia.
  • Mitochondrial function, ROS production, and gene expression were analyzed.
  • Cytotoxicity assays were performed against cancer cell lines and patient-derived organoids.
  • DRP1 function was modulated via pharmacological inhibition or CRISPR-Cas9 knockout.

Main Results:

  • Hypoxia reduced NK cell mitochondrial content and membrane potential, increased ROS, and altered gene expression.
  • Cytotoxic activity was significantly impaired, even with CAR engineering.
  • DRP1 inhibition or knockout restored mitochondrial function and preserved NK cell cytotoxicity under hypoxia.
  • DRP1 knockout CAR NK cells maintained efficacy against cancer cell lines in hypoxic conditions.

Conclusions:

  • DRP1 inactivation is a viable strategy to enhance NK cell function in the hypoxic tumor microenvironment.
  • Metabolic engineering approaches targeting DRP1 may improve CAR-NK cell therapy for solid tumors.