• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Tld1 是甘油三酯脂解的调节剂，可划分脂滴亚群。

Tld1 is a regulator of triglyceride lipolysis that demarcates a lipid droplet subpopulation.

机构信息

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

Department of Chemistry, University of Utah, Salt Lake City, UT, USA.

出版信息

J Cell Biol. 2024 Jan 1;223(1). doi: 10.1083/jcb.202303026. Epub 2023 Oct 27.

DOI:10.1083/jcb.202303026
PMID:37889293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10609110/
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.

摘要

细胞将脂质以甘油三酯（TG）和固醇酯（SE）的形式储存在脂滴（LD）中。存在不同的 LD 池，但一个普遍的问题是蛋白质如何定位到 LD 亚群并将功能传递给它们。在这里，我们表明酵母蛋白 YDR275W/Tld1（用于 TG 相关 LD 蛋白 1）定位于一组含有 TG 的 LD 上，并揭示它负调控脂解。在机制上，Tld1 LD 的靶向需要 TG，并且由两个不同的疏水区（HR）介导。分子动力学模拟表明，Tld1 的 HR 与 LD 上的 TG 相互作用，并在酵母和人类细胞中在富含 TG 的 LD 与富含 SE 的 LD 上采用特定构象。Tld1 缺陷型酵母在 LD 生物发生中没有缺陷，但表现出依赖于脂肪酶 Tgl3 的升高的 TG 脂解。值得注意的是，Tld1 的过表达而不是 LD 蛋白 Pln1/Pet10 的过表达促进了 TG 的积累，而不改变 SE 池。最后，我们发现 Tld1 缺陷型细胞在延长的酵母饥饿期间显示出 LD 动员的改变。我们提出 Tld1 感知富含 TG 的 LD，并调节 LD 亚群的脂解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/70a90ce81e08/JCB_202303026_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/af2fcd5d3958/JCB_202303026_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/3d03b1786441/JCB_202303026_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/0a77ce5e435a/JCB_202303026_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/4bb7c8b59a30/JCB_202303026_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/dcbfea50fb05/JCB_202303026_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/95a42503d940/JCB_202303026_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/6f3bb75cb614/JCB_202303026_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/beff161f5986/JCB_202303026_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/84ad64980899/JCB_202303026_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/98c8e54afe47/JCB_202303026_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/dd64ea32e912/JCB_202303026_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/03f969aa430d/JCB_202303026_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/0179f7991aa9/JCB_202303026_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/70a90ce81e08/JCB_202303026_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/af2fcd5d3958/JCB_202303026_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/3d03b1786441/JCB_202303026_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/0a77ce5e435a/JCB_202303026_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/4bb7c8b59a30/JCB_202303026_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/dcbfea50fb05/JCB_202303026_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/95a42503d940/JCB_202303026_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/6f3bb75cb614/JCB_202303026_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/beff161f5986/JCB_202303026_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/84ad64980899/JCB_202303026_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/98c8e54afe47/JCB_202303026_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/dd64ea32e912/JCB_202303026_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/03f969aa430d/JCB_202303026_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/0179f7991aa9/JCB_202303026_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f50/10609110/70a90ce81e08/JCB_202303026_Fig9.jpg

相似文献

1
Tld1 is a regulator of triglyceride lipolysis that demarcates a lipid droplet subpopulation.Tld1 是甘油三酯脂解的调节剂，可划分脂滴亚群。
J Cell Biol. 2024 Jan 1;223(1). doi: 10.1083/jcb.202303026. Epub 2023 Oct 27.
2
Tld1 is a novel regulator of triglyceride lipolysis that demarcates a lipid droplet subpopulation.Tld1是甘油三酯脂解的一种新型调节因子，它划分出一个脂滴亚群。
bioRxiv. 2023 Sep 11:2023.03.07.531595. doi: 10.1101/2023.03.07.531595.
3
Triglyceride lipolysis triggers liquid crystalline phases in lipid droplets and alters the LD proteome.甘油三酯脂解在脂滴中引发液晶相，并改变 LD 蛋白质组。
J Cell Biol. 2022 Nov 7;221(11). doi: 10.1083/jcb.202205053. Epub 2022 Sep 16.
4
Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting.Arf1/衣被蛋白I机制直接作用于脂滴，并使其与内质网相连以进行蛋白质靶向运输。
Elife. 2014;3:e01607. doi: 10.7554/eLife.01607. Epub 2014 Feb 4.
5
The hepatitis C virus core protein inhibits adipose triglyceride lipase (ATGL)-mediated lipid mobilization and enhances the ATGL interaction with comparative gene identification 58 (CGI-58) and lipid droplets.丙型肝炎病毒核心蛋白抑制脂肪甘油三酯脂肪酶（ATGL）介导的脂质动员，并增强ATGL与比较基因识别58（CGI-58）和脂滴的相互作用。
J Biol Chem. 2014 Dec 26;289(52):35770-80. doi: 10.1074/jbc.M114.587816. Epub 2014 Nov 7.
6
Molecular determinants of lipid droplet subpopulations and their fates.脂质滴亚群及其命运的分子决定因素。
FEBS Lett. 2024 May;598(10):1199-1204. doi: 10.1002/1873-3468.14891. Epub 2024 Apr 25.
7
A defect of the vacuolar putative lipase Atg15 accelerates degradation of lipid droplets through lipolysis.液泡假定脂肪酶Atg15的缺陷通过脂解作用加速脂滴的降解。
Autophagy. 2015;11(8):1247-58. doi: 10.1080/15548627.2015.1056969.
8
High confidence proteomic analysis of yeast LDs identifies additional droplet proteins and reveals connections to dolichol synthesis and sterol acetylation.对酵母脂滴进行的高可信度蛋白质组学分析鉴定出了其他脂滴蛋白，并揭示了其与多萜醇合成及甾醇乙酰化的关联。
J Lipid Res. 2014 Jul;55(7):1465-77. doi: 10.1194/jlr.M050229. Epub 2014 May 27.
9
Identification of motifs and mechanisms for lipid droplet targeting of the lipolytic inhibitors G0S2 and HIG2.鉴定脂肪滴靶向脂解抑制剂 G0S2 和 HIG2 的基序和机制。
J Cell Sci. 2022 Dec 15;135(24). doi: 10.1242/jcs.260236. Epub 2022 Dec 14.
10
Decoration of myocellular lipid droplets with perilipins as a marker for in vivo lipid droplet dynamics: A super-resolution microscopy study in trained athletes and insulin resistant individuals.肌细胞脂滴的 perilipin 修饰作为体内脂滴动力学的标志物：一项在训练有素的运动员和胰岛素抵抗个体中进行的超分辨率显微镜研究。
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Feb;1866(2):158852. doi: 10.1016/j.bbalip.2020.158852. Epub 2020 Nov 4.

引用本文的文献

1
Key enzymes involved in the utilization of fatty acids by : a review.参与脂肪酸利用的关键酶：综述
Front Microbiol. 2024 Jan 11;14:1294182. doi: 10.3389/fmicb.2023.1294182. eCollection 2023.

本文引用的文献

1
TmAlphaFold database: membrane localization and evaluation of AlphaFold2 predicted alpha-helical transmembrane protein structures.TmAlphaFold 数据库：AlphaFold2 预测的 α-螺旋跨膜蛋白结构的膜定位和评估。
Nucleic Acids Res. 2023 Jan 6;51(D1):D517-D522. doi: 10.1093/nar/gkac928.
2
Capturing the Liquid-Crystalline Phase Transformation: Implications for Protein Targeting to Sterol Ester-Rich Lipid Droplets.捕捉液晶相转变：对蛋白质靶向富含甾醇酯的脂滴的影响。
Membranes (Basel). 2022 Sep 28;12(10):949. doi: 10.3390/membranes12100949.
3
The Epigenetic Dimension of Protein Structure Is an Intrinsic Weakness of the AlphaFold Program.
蛋白质结构的表观遗传维度是 AlphaFold 程序的固有弱点。
Biomolecules. 2022 Oct 20;12(10):1527. doi: 10.3390/biom12101527.
4
Triglyceride lipolysis triggers liquid crystalline phases in lipid droplets and alters the LD proteome.甘油三酯脂解在脂滴中引发液晶相，并改变 LD 蛋白质组。
J Cell Biol. 2022 Nov 7;221(11). doi: 10.1083/jcb.202205053. Epub 2022 Sep 16.
5
Computational Studies of Lipid Droplets.脂质滴的计算研究。
J Phys Chem B. 2022 Mar 24;126(11):2145-2154. doi: 10.1021/acs.jpcb.2c00292. Epub 2022 Mar 9.
6
Ins and outs of AlphaFold2 transmembrane protein structure predictions.AlphaFold2 跨膜蛋白结构预测的来龙去脉。
Cell Mol Life Sci. 2022 Jan 15;79(1):73. doi: 10.1007/s00018-021-04112-1.
7
Recharging your fats: CHARMM36 parameters for neutral lipids triacylglycerol and diacylglycerol.为脂肪充电：中性脂质三酰甘油和二酰甘油的CHARMM36参数
Biophys Rep (N Y). 2021 Dec 8;1(2):None. doi: 10.1016/j.bpr.2021.100034.
8
Origin of gradients in lipid density and surface tension between connected lipid droplet and bilayer.相连脂滴与双层膜之间脂质密度和表面张力梯度的起源。
Biophys J. 2021 Dec 21;120(24):5491-5503. doi: 10.1016/j.bpj.2021.11.022. Epub 2021 Nov 19.
9
Accurate prediction of protein structures and interactions using a three-track neural network.使用三轨神经网络准确预测蛋白质结构和相互作用。
Science. 2021 Aug 20;373(6557):871-876. doi: 10.1126/science.abj8754. Epub 2021 Jul 15.
10
Highly accurate protein structure prediction with AlphaFold.利用 AlphaFold 进行高精度蛋白质结构预测。
Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.