Molecular Dissection of Bsc2: A Novel Negative Regulator of Triglyceride Lipolysis for a Lipid Droplet Subpopulation

Eukaryotic cells store lipids in the form of triglyceride (TG) and sterol-ester (SE) in cytoplasmic organelles called lipid droplets (LDs). Distinct pools of LDs with unique surface proteomes exist in cells, but a pervasive question is how proteins localize to and convey functions to specific LD subsets. Here, we show the yeast protein Bsc2 localizes to a specific subset of TG-containing LDs, and reveal it negatively regulates TG lipolysis. Mechanistically, Bsc2 LD targeting requires TG, and LD targeting is mediated by specific N-terminal hydrophobic regions (HRs) sufficient for Bsc2 function. Molecular dynamics simulations reveal these Bsc2 HRs interact extensively with TG on modeled LDs, and adopt a specific conformation on TG-rich LDs versus SE-rich LDs or a modeled ER bilayer. Bsc2-deficient yeast display no defect in LD biogenesis, but exhibit enhanced TG lipolysis dependent on the major TG lipase Tgl3. Remarkably, over-expression of Bsc2, but not LD protein Pln1, causes TG accumulation without altering SE levels. Finally, we find that Bsc2-deficient cells display altered LD accumulation during stationary phase growth. We propose that Bsc2 is a novel regulator of TG lipolysis that localizes to a subset of TG-enriched LDs and locally regulates TG lipolysis.

Author dc:creator

• Speer, Natalie Ortiz

Contributors dc:contributor

• Goodman, Joel M.
• Henne, W. Mike
• Friedman, Jonathan R.
• Nicastro, Daniela

• Lipid Droplets
• Lipolysis
• Saccharomyces cerevisiae Proteins

Language dc:language

en

Identifier

1417098750

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/10242