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甘油三酯脂解在脂滴中引发液晶相，并改变 LD 蛋白质组。

Triglyceride lipolysis triggers liquid crystalline phases in lipid droplets and alters the LD proteome.

机构信息

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX.

Department of Biology, University of Fribourg, Fribourg, Switzerland.

出版信息

J Cell Biol. 2022 Nov 7;221(11). doi: 10.1083/jcb.202205053. Epub 2022 Sep 16.

DOI:10.1083/jcb.202205053
PMID:36112368
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9485706/
Abstract

Lipid droplets (LDs) are reservoirs for triglycerides (TGs) and sterol-esters (SEs), but how these lipids are organized within LDs and influence their proteome remain unclear. Using in situ cryo-electron tomography, we show that glucose restriction triggers lipid phase transitions within LDs generating liquid crystalline lattices inside them. Mechanistically this requires TG lipolysis, which decreases the LD's TG:SE ratio, promoting SE transition to a liquid crystalline phase. Molecular dynamics simulations reveal TG depletion promotes spontaneous TG and SE demixing in LDs, additionally altering the lipid packing of the PL monolayer surface. Fluorescence imaging and proteomics further reveal that liquid crystalline phases are associated with selective remodeling of the LD proteome. Some canonical LD proteins, including Erg6, relocalize to the ER network, whereas others remain LD-associated. Model peptide LiveDrop also redistributes from LDs to the ER, suggesting liquid crystalline phases influence ER-LD interorganelle transport. Our data suggests glucose restriction drives TG mobilization, which alters the phase properties of LD lipids and selectively remodels the LD proteome.

摘要

脂滴 (LDs) 是甘油三酯 (TGs) 和甾醇酯 (SEs) 的储存库，但这些脂质在 LDs 中的组织方式以及它们如何影响其蛋白质组仍不清楚。使用原位冷冻电子断层扫描，我们表明葡萄糖限制会在 LDs 内引发脂质相变，从而在其中产生液晶晶格。从机制上讲，这需要 TG 脂解，它降低了 LD 的 TG:SE 比，促进 SE 向液晶相转变。分子动力学模拟表明，TG 耗尽会促进 LD 中 TG 和 SE 的自发分离，此外还会改变 PL 单层表面的脂质堆积。荧光成像和蛋白质组学进一步表明，液晶相与 LD 蛋白质组的选择性重塑有关。一些典型的 LD 蛋白，包括 Erg6，重新定位到 ER 网络，而其他蛋白仍然与 LD 相关。模型肽 LiveDrop 也从 LD 重新分配到 ER，这表明液晶相影响 ER-LD 细胞器间运输。我们的数据表明，葡萄糖限制会驱动 TG 动员，从而改变 LD 脂质的相性质，并选择性地重塑 LD 蛋白质组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/9c06c74795df/JCB_202205053_FigS6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/550320235d78/JCB_202205053_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/0986c3f093b4/JCB_202205053_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/1b831beb48c0/JCB_202205053_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/54c65c7f0d80/JCB_202205053_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/d7752cabf6de/JCB_202205053_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/8d4dc64c15ef/JCB_202205053_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/ec32d0487d7b/JCB_202205053_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/386693bb951c/JCB_202205053_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/809b5269eec5/JCB_202205053_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/de8099cb1175/JCB_202205053_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/3fd22efcbcac/JCB_202205053_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/9c06c74795df/JCB_202205053_FigS6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/550320235d78/JCB_202205053_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/0986c3f093b4/JCB_202205053_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/1b831beb48c0/JCB_202205053_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/54c65c7f0d80/JCB_202205053_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/d7752cabf6de/JCB_202205053_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/8d4dc64c15ef/JCB_202205053_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/ec32d0487d7b/JCB_202205053_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/386693bb951c/JCB_202205053_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/809b5269eec5/JCB_202205053_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/de8099cb1175/JCB_202205053_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/3fd22efcbcac/JCB_202205053_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0121/9485706/9c06c74795df/JCB_202205053_FigS6.jpg

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