Newly discovered lipid prevents cell death
Programmed cell death is an important tool that an organism uses to maintain good health. When a cell is not functioning as it should, various stress responses are activated. The goal of these reactions is to restore the original cellular function.
An example is autophagy, a process in which the cell partially digests itself to gain energy, which it can then use for its own repair. If these attempts fail, the cell dies. This allows the body to fight diseases such as diabetes, cancer, neurodegeneration and infections.
A double-edged sword
Stress responses, however, are a double-edged sword and must be kept in balance to benefit the body. This is why cells also contain substances that stop stress reactions and inhibit cell death.
An international consortium of research groups led by Andreas Koeberle from the Michael Popp Institute at the University of Innsbruck has now been able to prove that a membrane lipid called PI (18:1/18:1) is significantly involved in this process. The study, published in the research journal Nature Communicationopens up many interesting medical possibilities.
Stress by fatty acids
The regulation of stress responses involves many different enzymes. One of them is the SCD1 enzyme. It converts saturated fatty acids into unsaturated fatty acids and is therefore particularly effective against stress triggered by fats in harmful concentrations.
In principle, this process benefits the health of the organism. However, it can become dangerous if practiced excessively. Researchers have long established a clear link between SCD1 and inflammation, metabolic disease and cancer. The full functional scope of this enzyme is still unknown. Therefore, treatments that specifically inhibit SCD1 can cause serious side effects and are not approved for treatment.
The researchers have now been able to trace the stress-response inhibitory effect of SCD1 to an indirect product of this enzyme: the membrane lipid PI(18:1/18:1), which is largely composed of a fatty acid produced by SCD1.
A fundamental process deciphered
In the future, PI(18:1/18:1) could be specifically administered or its formation inhibited. This could fight disease without having to disrupt the full range of functions of the SCD1 enzyme. However, the full range of functions of PI(18:1/18:1) must first be carefully studied and understood.
“What is particularly interesting is that stress-associated processes, such as the aging process, resistance to chemotherapy or the development of tumors, all influence the amount of PI(18:1/18:1) in the affected tissues, a connection that opens up new therapeutic approaches,” says Andreas Koeberle.
“We have deciphered a very fundamental process with this study,” he adds. “It is an important starting point and sets new directions for further research.”
Natural products as a source of ideas
At the Michael Popp Institute at the University of Innsbruck, researchers are studying the molecular pharmacological effects of natural products of plant origin. The research work published today was initiated by the application of active plant substances.
“We wanted to find a primordial mechanism that takes place in the body, regardless of the pathway by which cell death occurs,” says Koeberle. “To do this, we used plant substances that have a toxic effect on cells, for example myrtucommulone A, which is obtained from myrtle. When this substance was added, we were able to observe clear changes in the composition of cellular lipids and that’s how we got the idea for this project, so in a way natural substances were the starting point to gather ideas and learn what happens in the cell human.
Publication: Thürmer, M., Gollowitzer, A., Pein, H. et al. PI(18:1/18:1) is an SCD1-derived lipokine that limits stress signaling. Common Nat 13, 2982 (2022). https://doi.org/10.1038/s41467-022-30374-9
Partner establishments: The participants from the University of Innsbruck were the Michael Popp Institute, the Institute of Biochemistry and the Center for Molecular Biosciences Innsbruck. Other research partners were Friedrich Schiller University Jena, University Hospital Jena, Max Planck Institute for Chemical Ecology, University Hospital Hamburg-Eppendorf, LMU Munich, University Salzburg Paracelsus Institute of Medicine, the Leibniz Institute for Aging Research, the University of Groningen, the University of Oldenburg and the University of Barcelona.
More information: The research was funded by the German Research Foundation, Center for Phospholipid Research, Universities of Jena and Innsbruck, Leibniz Institute for Aging Research, State of Thuringia, the Carl Zeiss Foundation, the Federal Ministry of Research and Development, the EU Horizon 2020 Research Framework Program and the Tyrolean Science Fund.
The title of the article
Thürmer, M., Gollowitzer, A., Pein, H. et al. PI(18:1/18:1) is an SCD1-derived lipokine that limits stress signaling. Common Nat 13, 2982 (2022).
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