"Lipid switches in cell physiology: From nutrient signals to disease"

Phosphoinositides (PIs) form a minor class of phospholipids with crucial functions in cell physiology, ranging from cell signalling and motility to a role as signposts of compartmental membrane identity and dynamics. In fed cells, phosphatidylinositol 3-phosphates are present at the plasma membrane and within the endolysosomal system, where they serve as key regulators of both cell signalling and of intracellular membrane dynamics, while PI 4-phosphates delineate the secretory pathway. In my talk I will discuss the localization, regulation, and molecular mechanism of action of PI 3-kinases and their roles in endocytosis and in nutrient signaling within the endolysosomal system. Moreover, I will cover our recent advances in the analysis of the metabolic pathways that regulate the cellular synthesis and turnover of distinct PI phosphates at endosomes or lysosomes in response to altering nutrient conditions, discuss the mechanisms by which these lipids regulate endolysosomal membrane dynamics and metabolism, and provide examples of how dysregulation of these pathways may cause human disease. Our data provide a framework for how PI phosphate metabolism is integrated into the cellular network and identify PI kinases as targets for future therapeutics.