Regulation of phospholipid remodeling in mitochondria

Lipid metabolism is chronically understudied and thus often oversimplified. Abnormal lipid compositions are causative for severe malfunctions leading to neurological disorders, cardiomyopathies and other pathologies. As starting point for this project we utilize rare diseases affecting lipid metabolism (e.g. Barth syndrome) as model systems, which however are likely only the tip of the iceberg. Although our core research question how membrane lipid alterations cause disease and vice versa is still largely unresolved, it is safe to assume that they play an important role in many disorders. Thus, a great challenge is linking the available comprehensive genetic and lipidomic information with its functional effects, also with the aim to develop novel therapeutic interventions. With this project we aim to revolutionize how lipid data are utilized to generate detailed functional insights into their regulation and interaction. In contrast to current approaches, our ground-breaking modeling concepts take into account the special traits of lipid metabolism (promiscuity, interconnectivity, redundancy). Coupled with our recently developed analytical and bioinformatics tools, this paves the way to actually understand lipid changes instead of only describing them. Importantly, these functional models provide extensive added value, as they are generally applicable, not restricted to the initial model diseases, and might change the way we understand lipids.