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脂质饱和度控制核膜功能。

Lipid saturation controls nuclear envelope function.

机构信息

Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria.

Center for Molecular Biology, University of Vienna, Vienna, Austria.

出版信息

Nat Cell Biol. 2023 Sep;25(9):1290-1302. doi: 10.1038/s41556-023-01207-8. Epub 2023 Aug 17.

DOI:10.1038/s41556-023-01207-8
PMID:37591950
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10495262/
Abstract

The nuclear envelope (NE) is a spherical double membrane with elastic properties. How NE shape and elasticity are regulated by lipid chemistry is unknown. Here we discover lipid acyl chain unsaturation as essential for NE and nuclear pore complex (NPC) architecture and function. Increased lipid saturation rigidifies the NE and the endoplasmic reticulum into planar, polygonal membranes, which are fracture prone. These membranes exhibit a micron-scale segregation of lipids into ordered and disordered phases, excluding NPCs from the ordered phase. Balanced lipid saturation is required for NPC integrity, pore membrane curvature and nucleocytoplasmic transport. Oxygen deprivation amplifies the impact of saturated lipids, causing NE rigidification and rupture. Conversely, lipid droplets buffer saturated lipids to preserve NE architecture. Our study uncovers a fundamental link between lipid acyl chain structure and the integrity of the cell nucleus with implications for nuclear membrane malfunction in ischaemic tissues.

摘要

核膜（NE）是具有弹性的球形双层膜。脂质化学如何调节 NE 的形状和弹性尚不清楚。在这里，我们发现脂质酰基链不饱和是 NE 和核孔复合物（NPC）结构和功能所必需的。增加脂质饱和度会使 NE 和内质网变得僵硬，形成平面多边形膜，这些膜容易断裂。这些膜在微米尺度上表现出脂质的有序和无序相的分离，将 NPC 排除在有序相之外。脂质饱和度的平衡对于 NPC 的完整性、核孔膜曲率和核质转运都是必需的。缺氧会放大饱和脂质的影响，导致 NE 僵化和破裂。相反，脂滴缓冲饱和脂质以维持 NE 结构。我们的研究揭示了脂质酰基链结构与细胞核完整性之间的基本联系，这对缺血组织中核膜功能障碍具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/33a2032ee95e/41556_2023_1207_Fig13_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/33a2032ee95e/41556_2023_1207_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/ceed7d901094/41556_2023_1207_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/6d6e2763193f/41556_2023_1207_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/e8c144b64c6b/41556_2023_1207_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/4463ad08b60c/41556_2023_1207_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/09c5900f4824/41556_2023_1207_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/f2e488686e4b/41556_2023_1207_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/4771296d4d85/41556_2023_1207_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/dbef6718a851/41556_2023_1207_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/e845256d61ff/41556_2023_1207_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/d51c39a0178e/41556_2023_1207_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/ce217443cb96/41556_2023_1207_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/230b7c690ec7/41556_2023_1207_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578f/10495262/33a2032ee95e/41556_2023_1207_Fig13_ESM.jpg

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