Cholesterol esters form supercooled lipid droplets whose nucleation is facilitated by triacylglycerols.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 02 2023
17 02 2023
Historique:
received:
27
07
2022
accepted:
27
01
2023
entrez:
22
2
2023
pubmed:
23
2
2023
medline:
25
2
2023
Statut:
epublish
Résumé
Cellular cholesterol can be metabolized to its fatty acid esters, cholesteryl esters (CEs), to be stored in lipid droplets (LDs). With triacylglycerols (TGs), CEs represent the main neutral lipids in LDs. However, while TG melts at ~4 °C, CE melts at ~44 °C, raising the question of how CE-rich LDs form in cells. Here, we show that CE forms supercooled droplets when the CE concentration in LDs is above 20% to TG and, in particular, liquid-crystalline phases when the fraction of CEs is above 90% at 37 °C. In model bilayers, CEs condense and nucleate droplets when the CE/phospholipid ratio reaches over 10-15%. This concentration is reduced by TG pre-clusters in the membrane that thereby facilitate CE nucleation. Accordingly, blocking TG synthesis in cells is sufficient to strongly dampen CE LD nucleation. Finally, CE LDs emerged at seipins, which cluster and nucleate TG LDs in the ER. However, when TG synthesis is inhibited, similar numbers of LDs are generated in the presence and absence of seipin, suggesting that seipin controls CE LD formation via its TG clustering capacity. Our data point to a unique model whereby TG pre-clusters, favorable at seipins, catalyze the nucleation of CE LDs.
Identifiants
pubmed: 36807572
doi: 10.1038/s41467-023-36375-6
pii: 10.1038/s41467-023-36375-6
pmc: PMC9938224
doi:
Substances chimiques
Cholesterol Esters
0
Triglycerides
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
915Informations de copyright
© 2023. The Author(s).
Références
Curr Opin Cell Biol. 2019 Aug;59:88-96
pubmed: 31075519
J Cell Biol. 2020 Apr 6;219(4):
pubmed: 32328636
Dev Cell. 2017 Jun 19;41(6):591-604.e7
pubmed: 28579322
Prog Lipid Res. 1984;23(3):135-67
pubmed: 6399750
Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):16866-16871
pubmed: 31375636
J Cell Biol. 2021 Oct 4;220(10):
pubmed: 34323918
Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):
pubmed: 33674387
J Comput Chem. 2013 Sep 30;34(25):2135-45
pubmed: 23832629
Dev Cell. 2019 Dec 2;51(5):551-563.e7
pubmed: 31708432
Hum Mol Genet. 2013 Mar 15;22(6):1157-66
pubmed: 23250914
EMBO Mol Med. 2013 Jul;5(7):973-83
pubmed: 23740690
STAR Protoc. 2020 Sep 25;1(3):100116
pubmed: 33377012
Nat Commun. 2016 Mar 18;7:11046
pubmed: 26988139
Nat Rev Mol Cell Biol. 2013 Dec;14(12):775-86
pubmed: 24220094
PLoS Biol. 2021 Jan 22;19(1):e3000998
pubmed: 33481779
Can J Biochem Physiol. 1959 Aug;37(8):911-7
pubmed: 13671378
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
pubmed: 8744570
Nat Struct Mol Biol. 2022 Mar;29(3):194-202
pubmed: 35210614
Mol Biol Cell. 2021 Jun 1;32(12):1147-1157
pubmed: 33826368
J Cell Sci. 2012 Sep 1;125(Pt 17):4067-76
pubmed: 22685330
J Chem Theory Comput. 2018 Jun 12;14(6):3342-3350
pubmed: 29750867
Elife. 2021 Feb 01;10:
pubmed: 33522484
Dev Cell. 2019 Aug 19;50(4):478-493.e9
pubmed: 31178403
Traffic. 2020 May;21(5):386-397
pubmed: 32144825
Methods Enzymol. 1983;98:241-60
pubmed: 6321901
J Cell Biol. 2016 Nov 21;215(4):515-529
pubmed: 27872254
Nat Commun. 2017 Mar 31;8:14858
pubmed: 28361956
Nat Rev Mol Cell Biol. 2019 Mar;20(3):137-155
pubmed: 30523332
Biophys J. 2021 Dec 21;120(24):5491-5503
pubmed: 34808099
Biophys J. 2021 Feb 16;120(4):607-617
pubmed: 33460598
Elife. 2016 Aug 26;5:
pubmed: 27564575
Dev Cell. 2018 Oct 22;47(2):248-256.e4
pubmed: 30293840
J Biol Chem. 2010 Feb 26;285(9):6127-33
pubmed: 20032462
Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25440-25445
pubmed: 31772016
PLoS One. 2010 Sep 22;5(9):e12811
pubmed: 20877640
J Comput Chem. 2009 Jul 30;30(10):1545-614
pubmed: 19444816
J Comput Chem. 2008 Aug;29(11):1859-65
pubmed: 18351591
J Chem Inf Model. 2021 Feb 22;61(2):831-839
pubmed: 33442985
Food Chem. 2022 Oct 1;390:133202
pubmed: 35580521
J Cell Biol. 2022 Sep 5;221(9):
pubmed: 35938957
Trends Cell Biol. 2021 Feb;31(2):108-118
pubmed: 33293168
Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2205475119
pubmed: 35939716
Curr Biol. 2020 Jul 6;30(13):2481-2494.e6
pubmed: 32442467
Nat Commun. 2021 Oct 8;12(1):5892
pubmed: 34625558
Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3):
pubmed: 21421923
J Cell Biol. 2018 Dec 3;217(12):4080-4091
pubmed: 30327422
J Phys Chem B. 2010 Jun 17;114(23):7830-43
pubmed: 20496934
J Chem Theory Comput. 2011 Oct 11;7(10):3162-3180
pubmed: 22125473
Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20890-5
pubmed: 18093937
Biochim Biophys Acta. 2016 Aug;1861(8 Pt A):715-22
pubmed: 27131867
Curr Opin Cell Biol. 2019 Apr;57:64-70
pubmed: 30476754
Prog Lipid Res. 2019 Jul;75:100989
pubmed: 31351098
EMBO J. 2016 Dec 15;35(24):2699-2716
pubmed: 27879284
J Lipid Res. 2017 Jun;58(6):1067-1079
pubmed: 28404639
Genome Biol. 2006;7(10):R100
pubmed: 17076895
Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Oct;1862(10 Pt B):1260-1272
pubmed: 28735096