Lipids build cell membranes and organelles, some of which are signaling molecules, and are essential for regulating cellular function. Lipids are also a source of energy, but their excessive accumulation in the body can lead to obesity. Obesity is a major global problem, and using traditional methods such as exercise and diet may not always work. Fortunately, science can provide useful solutions based on the details of fat metabolism. Lipid metabolism involves the aided lipid synthesis and decomposition of multiple enzymes, thereby regulating the entire process. By understanding how these enzymes work, new methods can be developed for the treatment of obesity and other diseases related to lipid metabolism.
A team led by Professor Katarzyna Kwiatkowska from the Nencki Institute of Experimental Biology in Warsaw conducted a breakthrough study to shed light on a previously unknown mechanism that regulates the performance of enzymes involved in lipid metabolism. The team consisted of Gabriela Traczyk, Aneta Hromada-Judycka, Annaświątkowska, Anna Ciesielska and Julia Wiśniewska, and each played an important role in this discovery. Their findings, published in the Journal of Lipid Research, represent a significant advance in understanding cellular signaling and lipid metabolism.
Scientists use complex techniques to point out specific modifications of diacylglycerol kinase-ε (DGKε) molecules, s– Calciumyl diacylation, which includes the addition of fatty acids (palmitic acid, a common ingredient in dietary fats) to the enzyme. These rigorous methods include changing the cloning of the DGKε variant with a single amino acid residue relative to the natural form, transfecting DGKε into cultured human kidney cells, and utilizing specialized chemistry techniques based on click chemistry. These techniques emphasize the accuracy and thoroughness of the research, resulting in solid and reliable results.
Professor Kwiatkowska explained: “In our study, we first discovered the specific cysteines experienced.” s– The content in dgkε. This amino acid is located on the cytoplasmic side of DGKε integrated into the organellar membrane. We then used two complementary labeling (acyl polymethylethylene glycol and acyl biotin) techniques to reveal the execution enzyme (called ZDHHC) s-Palmitoylation. We found reliable proof of DGKε s– Calcium acylation of diacylglycerol to phosphatidic acid, which is a critical step in synthesis of certain lipids.
Scientists also used micelles of diacylglycerol to check the activity of the study enzyme, revealing that DGKε activity was reduced. s-Palmitoylation. Micellars are small spherical structures formed by molecules such as diacylglycerol, with hydrophobic and hydrophilic regions in aqueous solutions. The researchers also examined the cellular localization of DGKε, and in addition to the expected detection of DGKε in the endoplasmic reticulum where most lipids synthesize, they also found kinases in the Golgi body. They speculate sCell transport and localization of DGKε.
Master Traczyk explained: “Our findings indicate a small pool of DGKε in the Golgi, which leads us to propose specific aspects of its involvement in lipid synthesis. Although further studies of natural DGKε can reveal the exact role of DGKε in the Golgi , but our study opens new avenues for the study of this enzyme’s involvement in octanol phosphate signaling cycles and general lipid metabolism.”
This groundbreaking study conducted by the Kwiatkowska team shows that s– Calciumyl diacylation can fine-tune DGKε activity in specific cell chambers. This will greatly improve our understanding of cellular signaling and lipid metabolism and pave the way for novel therapeutic strategies for obesity and other diseases.
Journal Reference
Gabriela Traczyk, Aneta Hromada-Judycka, Annaświątkowska, Julia Wiśniewska, Anna Ciesielska, Katarzyna Kwiatkowska. “Diacylglycerol kinase-ε is acylated by S-methylbis on the cysteine at the cytoplasmic end of its N-terminal transmembrane fragment.” Journal of Lipid Research 65(1) (2023) 100480. doi: https://doi.org/10.1016/j.jlr.2023.100480
About the Author
Gabriela Traczyk She has a PhD and works in the Molecular Membrane Biology Laboratory at the Nencki Institute of Experimental Biology in Warsaw. Her research focuses on the function of DGKε kinase. Mutations in the gene encoding DGKε lead to a kidney disease called hemolytic uremic syndrome (AHUS), and Ms. Traczyk’s study aims to elucidate the effects of these mutations on the stability and enzymatic activity of DGKε. She is also the principal co-author of the study s– content of dgkε (orcID:
Aneta Hromada-Judyckaa postdoctoral researcher in the Molecular Membrane Biology Laboratory at the Institute of Experimental Biology, Warsaw. She received her PhD in 2011 and joined the laboratory in 2013. Her research focuses on elucidating the molecular mechanisms of TLR4 signaling. TLR4 is a plasma membrane receptor activated by bacterial lipopolysaccharide (LPS) during infection, and uncontrolled TLR4 activity can lead to sepsis. Dr. Hromada-Judycka has studied the effects of lipids (especially phosphatidylinositol derivatives) in the signaling cascade of TLR4 receptors. She is co-author of a proteomic study on protein palmitoylation in LPS-stimulated macrophages, which showed that DGKε kinase is one of the enzymes that control phosphatidylinositol levels. s-Palmitoylation. Dr. Hromada-Judycka is the result of the discovery (OrcID::
