An international consortium led by Austria’s University of Innsbruck has been able to show that a membrane lipid called PI(18:1/18:1) is significantly involved in the inhibition of cell death—findings that could have broad applications in aging, inflammation, cancer, and metabolic diseases.
Programmed cell death is an important tool that an organism uses to keep itself healthy. When a cell does not function as it should, various stress reactions are activated. The goal of these reactions is to restore the original cell function. One 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 should fail, the cell dies. This allows the body to fight diseases such as diabetes, cancer, neurodegeneration and infections.
Such stress responses, however, must be kept in balance to be beneficial to the body. That is why cells also contain substances that stop stress reactions and inhibit cell death.
The regulation of stress reactions involves many different enzymes. One such enzyme, SCD1, converts saturated fatty acids into unsaturated ones and is therefore particularly effective against stress that is triggered by fats in harmful concentrations. Researchers have long seen a clear connection between SCD1 and inflammation, metabolic diseases and cancer, but full functional scope of the enzyme is still unknown. Therefore, treatments that specifically inhibit SCD1 can lead to severe side effects and are not approved for therapy.
But Andreas Koeberle of the Michael Popp Institute at University of Innsbruck and colleagues report in Nature Communications that they have traced the stress response-inhibiting effect of SCD1 back to an indirect product of this enzyme—membrane lipid PI (18:1/18:1), which is largely composed of a fatty acid produced by SCD1. "What is particularly interesting is that stress-associated processes, such as the ageing process, resistance to chemotherapy or the development of tumors, all influence the amount of PI(18:1/18:1) in the affected tissues. There is a clear connection that opens up new therapeutic approaches," says Koeberle.
In the future, PI(18:1/18:1) could be specifically administered or its formation inhibited. This could fight diseases without having to disrupt the full range of functions of the enzyme SCD1. However, the whole range of PI(18:1/18:1)’s functions must first be thoroughly researched and understood. "We have deciphered a very fundamental process with this study," he adds. "It’s a significant starting point and sets new directions for further research."