Systematic analysis of tethered lipid droplet subpopulations

• Applicant: Professorin Dr. Maria Bohnert
• Subject Area: Cell Biology ; Biochemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 538651361

Lipid droplets (LDs) are ubiquitous lipid storage organelles that act as hubs of lipid metabolism and fulfil a range of further functions. To master their tasks, LDs need to communicate tightly with the other organelles that all depend on a continuous lipid flux. It is emerging that LDs communicate mainly via contact sites, structures that physically tether them to partner organelles. We have recently identified the protein machinery that forms vacuole lipid droplet (vCLIP) contact sites in Saccharomyces cerevisiae. Intriguingly, only a subpopulation of the cellular LD pool is engaged in vCLIPs in exponentially growing cells. These vCLIP-engaged LDs have a unique proteome and a special metabolic fate. In this project, we will investigate the functional roles of the vCLIP-engaged LD subpopulation and uncover how subpopulation-specificity of vCLIP is controlled. Importantly, we observe that contact site-based LD heterogeneity is not restricted to vCLIP, but a universal phenomenon. Using fluorescent tools for contact site detection, we can visualize LD subpopulations engaged in contacts with distinct partner organelles. We will use genetic and proteomic screening approaches to investigate the relationship between contact site formation and structural and functional LD heterogeneity, to identify the proteins that mediate subpopulation formation, and to uncover subpopulation-specific roles. Throughout the project, we will assess conservation of these processes in mammalian cells.

• DFG Programme: Research Units
• Subproject of: FOR 5815: Structural and functional lipid droplet heterogeneity