Tld1 is a regulator of triglyceride lipolysis that demarcates a lipid droplet subpopulation
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Abstract
Cells store lipids in the form of triglyceride (TG) and sterol ester (SE) in lipid droplets (LDs). Distinct pools of LDs exist, but a pervasive question is how proteins localize to and convey functions to LD subsets. Here, we show that the yeast protein YDR275W/Tld1 (for TG-associated LD protein 1) localizes to a subset of TG-containing LDs and reveal it negatively regulates lipolysis. Mechanistically, Tld1 LD targeting requires TG, and it is mediated by two distinct hydrophobic regions (HRs). Molecular dynamics simulations reveal that Tld1’s HRs interact with TG on LDs and adopt specific conformations on TG-rich LDs versus SE-rich LDs in yeast and human cells. Tld1-deficient yeast display no defect in LD biogenesis but exhibit elevated TG lipolysis dependent on lipase Tgl3. Remarkably, overexpression of Tld1, but not LD protein Pln1/Pet10, promotes TG accumulation without altering SE pools. Finally, we find that Tld1-deficient cells display altered LD mobilization during extended yeast starvation. We propose that Tld1 senses TG-rich LDs and regulates lipolysis on LD subpopulations.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Ins and outs of AlphaFold2 transmembrane protein structure predictions
Hegedűs, T., Geisler, M., Lukács, G. L., & Farkas, B. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04112-1 · Cited by 127 · see citing works
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- Authors
- Speer, N. O., Braun, R. J., Reynolds, E. G., Brudnicka, A., Swanson, J. M. J., & Henne, W. M.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Utah (US)
- Corresponding author
- Henne, W. Mike
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2023-10-27
- Volume
- 223
- Issue
- 1
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC10609110
- OpenAlex
- W4387966519
- Cited by
- 19
- References
- 2
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 5
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Journal of Cell Biology (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- Welch Foundation (I-1873)
- National Institutes of Health (GM119768)
- National Institute of General Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases (DK126887)
- Ara Parseghian Medical Research Fund
- UT Southwestern Endowed Scholars Program
- Pittsburgh Supercomputing Center (MCB210016P)
- San Diego Supercomputing Center (MCB200018)
- National Science Foundation (#2138259, #2138286, #2138307, #2137603, #2138296)
- University of Utah
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- lipid droplets, lipolysis, triglycerides, hydrophobic region, lipid droplet formation, starvation, yeast, molecular dynamics simulation
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