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

Simple item page
dc.contributor.advisorGoodman, Joel M.en
dc.contributor.committeeMemberHenne, W. Mikeen
dc.contributor.committeeMemberFriedman, Jonathan R.en
dc.contributor.committeeMemberNicastro, Danielaen
dc.creatorSpeer, Natalie Ortizen
dc.creator.orcid0000-0002-0982-3025
dc.date.accessioned2024-01-11T20:20:56Z
dc.date.available2024-01-11T20:20:56Z
dc.date.created2023-12
dc.date.issuedDecember 2023
dc.date.submittedDecember 2023
dc.date.updated2024-01-11T20:20:57Z
dc.description.abstractEukaryotic 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.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1417098750
dc.identifier.urihttps://hdl.handle.net/2152.5/10242
dc.language.isoenen
dc.subjectLipid Dropletsen
dc.subjectLipolysisen
dc.subjectSaccharomyces cerevisiae Proteinsen
dc.titleMolecular Dissection of Bsc2: A Novel Negative Regulator of Triglyceride Lipolysis for a Lipid Droplet Subpopulationen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineCell and Molecular Biologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
SPEER-PRIMARY-2023.pdf
Size:
2.18 MB
Format:
Adobe Portable Document Format
Download

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.99 KB
Format:
Plain Text
Description:
Download

Collections

UT Southwestern Graduate School of Biomedical Sciences