» Articles » PMID: 21982710

Phosphatidylcholine Synthesis for Lipid Droplet Expansion is Mediated by Localized Activation of CTP:phosphocholine Cytidylyltransferase

Overview
Journal Cell Metab
Publisher Cell Press
Date 2011 Oct 11
PMID 21982710
Citations 240
Authors
Affiliations
Soon will be listed here.
Abstract

Lipid droplets (LDs) are cellular storage organelles for neutral lipids that vary in size and abundance according to cellular needs. Physiological conditions that promote lipid storage rapidly and markedly increase LD volume and surface. How the need for surface phospholipids is sensed and balanced during this process is unknown. Here, we show that phosphatidylcholine (PC) acts as a surfactant to prevent LD coalescence, which otherwise yields large, lipolysis-resistant LDs and triglyceride (TG) accumulation. The need for additional PC to coat the enlarging surface during LD expansion is provided by the Kennedy pathway, which is activated by reversible targeting of the rate-limiting enzyme, CTP:phosphocholine cytidylyltransferase (CCT), to growing LD surfaces. The requirement, targeting, and activation of CCT to growing LDs were similar in cells of Drosophila and mice. Our results reveal a mechanism to maintain PC homeostasis at the expanding LD monolayer through targeted activation of a key PC synthesis enzyme.

Citing Articles

Phosphatidylcholine Cytidine Transferase α (CCTα) Affects LD Formation Through Fusion and Lipophagy in Bovine Mammary Epithelial Cells.

Yang J, Fan Y, Kang F, Yang Y, Wang Y, Liu Y Int J Mol Sci. 2025; 26(5).

PMID: 40076755 PMC: 11901133. DOI: 10.3390/ijms26052135.


ANGPTL3 regulates the peroxisomal translocation of SmarcAL1 in response to cell growth states.

Nagai T, Mizoguchi T, Wang Y, Deik A, Bullock K, Clish C Sci Rep. 2025; 15(1):5036.

PMID: 39934259 PMC: 11814109. DOI: 10.1038/s41598-025-89552-6.


Lipid Metabolic Heterogeneity during Early Embryogenesis Revealed by Hyper-3D Stimulated Raman Imaging.

Huang J, Zhang L, Shao N, Zhang Y, Xu Y, Zhou Y Chem Biomed Imaging. 2025; 3(1):15-24.

PMID: 39886225 PMC: 11775849. DOI: 10.1021/cbmi.4c00055.


Reduced phosphatidylcholine synthesis suppresses the embryonic lethality of seipin deficiency.

Zhu J, Lam S, Yang L, Liang J, Ding M, Shui G Life Metab. 2025; 1(2):175-189.

PMID: 39872351 PMC: 11749705. DOI: 10.1093/lifemeta/loac021.


Lipid droplets in central nervous system and functional profiles of brain cells containing lipid droplets in various diseases.

Zhang L, Zhou Y, Yang Z, Jiang L, Yan X, Zhu W J Neuroinflammation. 2025; 22(1):7.

PMID: 39806503 PMC: 11730833. DOI: 10.1186/s12974-025-03334-5.


References
1.
Houweling M, Jamil H, Hatch G, Vance D . Dephosphorylation of CTP-phosphocholine cytidylyltransferase is not required for binding to membranes. J Biol Chem. 1994; 269(10):7544-51. View

2.
Tilley D, Evans C, Larson T, Edwards K, Friesen J . Identification and characterization of the nuclear isoform of Drosophila melanogaster CTP:phosphocholine cytidylyltransferase. Biochemistry. 2008; 47(45):11838-46. DOI: 10.1021/bi801161s. View

3.
Henneberry A, Wistow G, McMaster C . Cloning, genomic organization, and characterization of a human cholinephosphotransferase. J Biol Chem. 2000; 275(38):29808-15. DOI: 10.1074/jbc.M005786200. View

4.
Nishino N, Tamori Y, Tateya S, Kawaguchi T, Shibakusa T, Mizunoya W . FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets. J Clin Invest. 2008; 118(8):2808-21. PMC: 2483680. DOI: 10.1172/JCI34090. View

5.
Yao Z, Jamil H, Vance D . Choline deficiency causes translocation of CTP:phosphocholine cytidylyltransferase from cytosol to endoplasmic reticulum in rat liver. J Biol Chem. 1990; 265(8):4326-31. View