Triacylglycerol Synthesis Enzymes Mediate Lipid Droplet Growth by Relocalizing from the ER to Lipid Droplets
Open accessAbstract
Lipid droplets (LDs) store metabolic energy and membrane lipid precursors. With excess metabolic energy, cells synthesize triacylglycerol (TG) and form LDs that grow dramatically. It is unclear how TG synthesis relates to LD formation and growth. Here, we identify two LD subpopulations: smaller LDs of relatively constant size, and LDs that grow larger. The latter population contains isoenzymes for each step of TG synthesis. Glycerol-3-phosphate acyltransferase 4 (GPAT4), which catalyzes the first and rate-limiting step, relocalizes from the endoplasmic reticulum (ER) to a subset of forming LDs, where it becomes stably associated. ER-to-LD targeting of GPAT4 and other LD-localized TG synthesis isozymes is required for LD growth. Key features of GPAT4 ER-to-LD targeting and function in LD growth are conserved between Drosophila and mammalian cells. Our results explain how TG synthesis is coupled with LD growth and identify two distinct LD subpopulations based on their capacity for localized TG synthesis.
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DGAT2 is localized around lipid droplets where it is required for triacylglycerol synthesis.
“DGAT2 is localized around LDs where it is required for TG synthesis51,52,53.”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [51]
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- Authors
- Wilfling, F., Wang, H., Haas, J. T., Krahmer, N., Gould, T. J., Uchida, A., Cheng, J.-X., Graham, M., Christiano, R., Fröhlich, F., Liu, X., Buhman, K. K., Coleman, R. A., Bewersdorf, J., Farese, R. V., & Walther, T. C.
- Affiliations
- Yale University (US)
- Gladstone Institutes (US)
- Purdue University West Lafayette (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Walther, Tobias C.
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 24
- Issue
- 4
- Pages
- 384-399
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC3727400
- OpenAlex
- W1997238838
- Cited by
- 806
- References
- 1
- Citations by year
- 2026: 45 · 2025: 63 · 2024: 60 · 2023: 69 · 2022: 49 · 2021: 71 · 2020: 82 · 2019: 63 · 2018: 62 · 2017: 66 · 2016: 60 · 2015: 54 · 2014: 36 · 2013: 25
- FWCI
- 27.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 389 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- UNC Libraries
- Funders
- Gladstone Institutes
- National Institute of General Medical Sciences (F32GM096859)
- American Historical Association (0835203 N, 11PRE5140017)
- 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, triglyceride synthesis, GPAT4, glycerol-3-phosphate acyltransferase, endoplasmic reticulum, lipid droplet growth, isozymes, Drosophila, fat deposition
- MeSH terms
- Animals, Cells, Cultured, Embryo, Mammalian, Endoplasmic Reticulum, Fibroblasts, Glycerol-3-Phosphate O-Acyltransferase, Lipids, Mice, Transgenic, Phospholipids, Triglycerides, Immunoblotting, Mice, Knockout, Immunoprecipitation, Lipid Metabolism, Diacylglycerol O-Acyltransferase, Mice
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