How Itaconate Travels Through Space and Time to Shape Our Immune Response

GPS tracker for molecules

“We know that cells produce high amounts of itaconate to alter immune responses, and we were interested in whether cells recycle it to fuel metabolic processes,” says Professor Cordes. To track where itaconate travels in the body and how cells break it down, the interdisciplinary team used specially labeled itaconate. “Our tracing approach is similar to putting a GPS tracker on a car to follow its journey. We use non-toxic stable isotopic tracer technology combined with mass spectrometry methods to track molecules like itaconate within the complex metabolic pathways of living organisms,” explains Hanna Willenbockel, a member of the Cordes research team and first author of the study.

A substance with many roles

Using this technology, the team discovered that most itaconate is rapidly filtered out of circulation through the kidneys. Some itaconate is converted into key metabolic intermediates such as acetyl-CoA and mesaconate, and it also becomes part of the citric acid cycle in mitochondria. Additionally, it is transformed into a compound called itaconyl-coenzyme A, which influences enzymes involved in energy production and amino acid processing.

The research team has demonstrated in previous studies that itaconate reversibly inhibits the enzyme succinate dehydrogenase that reduces cellular damage associated with reoxygenation. “Our pharmacokinetic studies with itaconate highlight how it dynamically regulates succinate dehydrogenase and other key enzymes as well as overall metabolic processes. Scientists are looking into how itaconate could be used to treat diseases, and our findings might help create better treatments in the future,” says Cordes. However, the researchers caution that it is premature to take itaconate supplements to influence immune responses and that further studies are needed which may take several years.