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质膜可及胆固醇受ACC1和脂滴调控。

Plasma membrane accessible cholesterol is regulated by ACC1 and lipid droplets.

作者信息

Wijesinghe Kalani M, Kim Chai-Wan, Schad Emily O, Li Shuo, Chen Summer, Takeshima Erin, Khandwala Chandni B, Tillo Desiree, Lebensohn Andres M, Olzmann James A, Rohatgi Rajat, Kinnebrew Maia

机构信息

Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Center for Human Nutrition and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.

出版信息

bioRxiv. 2025 Aug 26:2025.08.21.671640. doi: 10.1101/2025.08.21.671640.

DOI:10.1101/2025.08.21.671640
PMID:40909529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12407704/
Abstract

Proper maintenance of plasma membrane (PM) cholesterol is essential for diverse processes ranging from animal development to pathogen evasion. Despite decades of study, the mechanisms governing cellular cholesterol regulation are incomplete. Using genome-wide screens we find that ACC1, the rate-limiting enzyme in fatty acid biosynthesis, regulates PM cholesterol transport. ACC1 loss causes a ~10-fold increase in PM accessible cholesterol in cells and mice. Mechanistically, we find that ACC1 regulates lipid droplet (LD) catabolism, and LDs are intimately tied to PM accessible cholesterol levels since reductions or elevations in their numbers block or promote cholesterol trafficking, respectively. Furthermore, LDs are required for cholesterol trafficking induced by 25-hydroxycholesterol, a modulator of inflammation and an interferon-stimulated second messenger that protects cells from pathogen invasion. This work identifies an unrecognized role for ACC1 and LDs in cholesterol regulation, which has implications for diseases where LD numbers are altered, from metabolic syndromes to neurodegeneration.

摘要

维持质膜（PM）胆固醇的正常水平对于从动物发育到病原体逃避等多种生理过程至关重要。尽管经过了数十年的研究，但细胞胆固醇调节机制仍不完整。通过全基因组筛选，我们发现脂肪酸生物合成的限速酶ACC1可调节质膜胆固醇转运。ACC1缺失会导致细胞和小鼠质膜可及胆固醇增加约10倍。从机制上讲，我们发现ACC1调节脂滴（LD）分解代谢，并且脂滴与质膜可及胆固醇水平密切相关，因为脂滴数量的减少或增加分别会阻碍或促进胆固醇运输。此外，25-羟基胆固醇（一种炎症调节剂和干扰素刺激的第二信使，可保护细胞免受病原体入侵）诱导的胆固醇运输需要脂滴。这项研究确定了ACC1和脂滴在胆固醇调节中一个未被认识的作用，这对脂滴数量改变的疾病（从代谢综合征到神经退行性疾病）具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/c8c9928f0c31/nihpp-2025.08.21.671640v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/d8fedc9ed7ce/nihpp-2025.08.21.671640v2-f0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/63ff20614b36/nihpp-2025.08.21.671640v2-f0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/da02c7c2471b/nihpp-2025.08.21.671640v2-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/63f4558af8ee/nihpp-2025.08.21.671640v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/99ef02054fd5/nihpp-2025.08.21.671640v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/743232de5b90/nihpp-2025.08.21.671640v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/339ca65d0994/nihpp-2025.08.21.671640v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/b3f04aa96335/nihpp-2025.08.21.671640v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/c8c9928f0c31/nihpp-2025.08.21.671640v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/d8fedc9ed7ce/nihpp-2025.08.21.671640v2-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/3ecabd9bf302/nihpp-2025.08.21.671640v2-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/63ff20614b36/nihpp-2025.08.21.671640v2-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/0e37184d2824/nihpp-2025.08.21.671640v2-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/08067eca8936/nihpp-2025.08.21.671640v2-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/da02c7c2471b/nihpp-2025.08.21.671640v2-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/63f4558af8ee/nihpp-2025.08.21.671640v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/99ef02054fd5/nihpp-2025.08.21.671640v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/743232de5b90/nihpp-2025.08.21.671640v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/339ca65d0994/nihpp-2025.08.21.671640v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/b3f04aa96335/nihpp-2025.08.21.671640v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7734/12407704/c8c9928f0c31/nihpp-2025.08.21.671640v2-f0006.jpg

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本文引用的文献

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2
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Sci Adv. 2025 Feb 21;11(8):eadu3194. doi: 10.1126/sciadv.adu3194. Epub 2025 Feb 19.
3
Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase.细丝结构揭示了人类乙酰辅酶 A 羧化酶的动态组织。
Sci Adv. 2024 Oct 11;10(41):eado4880. doi: 10.1126/sciadv.ado4880. Epub 2024 Oct 9.
4
Perilipin membrane integration determines lipid droplet heterogeneity in differentiating adipocytes. perilipin 膜的整合决定了分化脂肪细胞中脂滴的异质性。
Cell Rep. 2024 Apr 23;43(4):114093. doi: 10.1016/j.celrep.2024.114093. Epub 2024 Apr 10.
5
APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia.载脂蛋白 E4/4 与阿尔茨海默病小胶质细胞中的脂滴损伤有关。
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6
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J Exp Med. 2024 Apr 1;221(4). doi: 10.1084/jem.20232000. Epub 2024 Mar 1.
7
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Sci Transl Med. 2024 Feb 28;16(736):eadf9874. doi: 10.1126/scitranslmed.adf9874.
8
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9
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