ALW Open Programma aanvraag was awarded to Prof. Ody C.M. Sibon.

with project: Identification of external sources of Coenzyme A for cells and organisms

Coenzyme A was discovered more than 60 years ago and is mostly known for its essential role in metabolic reactions in the cell, among which, the reactions of the Krebs cycle are the better known. Recently, it was demonstrated that Coenzyme A is also involved in other cellular events such as signal transduction and posttranslational protein modifications. This further underscored the importance of Coenzyme A for all living organisms. Despite its discovery already in the middle of the previous century, Coenzyme A is still surrounded by mysteries, most likely because it is technically challenging to measure Coenzyme A and its precursors in a sensitive manner. We have developed sensitive detection methods for Coenzyme A and Coenzyme A-related molecules and by using stable labeled precursors of Coenzyme A and validated Drosophila melanogaster models, we demonstrated the presence of a so far unknown route for eukaryotic cells and organisms to obtain Coenzyme A. Our preliminary data now suggests the flow of Coenzyme A and/or Coenzyme A-precursors between organisms, such as from  the mother to progeny or from microbiome to the host or from food to the consumer. Here, we propose to investigate these flows and by doing so, to investigate the physiological relevance of our previously discovered novel route for cells and organisms to obtain Coenzyme A. Demonstrating a physiological role and understanding this pathway is important because it will change fundamental concepts of Coenzyme A homeostasis and may provide a treatment strategy for patients suffering from inborn-errors of Coenzyme A metabolism.