Abstract - Hummer

Organellar membranes have distinct compositional identities, which are critical for their function in living cells. To establish the chemical characteristics of the lipid bilayers requires the action of elaborate molecular machineries. In my presentation I will describe the complex processes giving autophagic membranes their identity. Macroautophagy (in short, autophagy) is a housekeeping process used by cells, e.g., to remove and recycle damaged organelles, toxic aggregates, or invading pathogens. The cargo is engulfed by the phagophore, a cup-shaped membraned, that then closes into a double-membrane vesicle, the autophagosome. Membrane fusion with a lysosome delivers the cargo for degradation. As the phagophore is formed from various lipid sources, its chemical characteristics are established first by the action of the membrane-acting class III phosphatidylinositol (PI) 3-kinase complex 1 (PI3KC3-C1). The resulting PI(3)P lipids help to recruit the downstream machinery. Early among these is the ATG16 complex, which further modifies the membrane by the covalent attachment of the ubiquitin-like LC3 proteins to phosphatidylethanolamine (PE) lipids, in a process akin to the action of E3 ligases. The LC3 proteins then bind to the autophagic cargo either directly or via cargo receptors. In my presentation, I will demonstrate how molecular dynamics simulations have helped us to elucidate the mechanisms by which PI3KC3-C1 and ATG16 complexes are activated on the membrane for PI phosphorylation and lipidation, respectively.