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Small lipid droplets are rigid enough to indent a nucleus, dilute the lamina, and cause rupture
The Journal of Cell Biology Pub Date : 2023-05-22 , DOI: 10.1083/jcb.202208123
Irena L Ivanovska 1 , Michael P Tobin 1 , Tianyi Bai 1 , Lawrence J Dooling 1 , Dennis E Discher 1
Affiliation  

The nucleus in many cell types is a stiff organelle, but fat-filled lipid droplets (FDs) in cytoplasm are seen to indent and displace the nucleus. FDs are phase-separated liquids with a poorly understood interfacial tension γ that determines how FDs interact with other organelles. Here, micron-sized FDs remain spherical as they indent peri-nuclear actomyosin and the nucleus, while causing local dilution of Lamin-B1 independent of Lamin-A,C and sometimes triggering nuclear rupture. Focal accumulation of the cytosolic DNA sensor cGAS at the rupture site is accompanied by sustained mislocalization of DNA repair factors to cytoplasm, increased DNA damage, and delayed cell cycle. Macrophages show FDs and engulfed rigid beads cause similar indentation dilution. Spherical shapes of small FDs indicate a high γ, which we measure for FDs mechanically isolated from fresh adipose tissue as ∼40 mN/m. This value is far higher than that of protein condensates, but typical of oils in water and sufficiently rigid to perturb cell structures including nuclei.

中文翻译:

小脂滴的刚性足以压入细胞核,稀释细胞核,并导致破裂

许多细胞类型的细胞核是坚硬的细胞器,但细胞质中充满脂肪的脂滴 (FD) 会凹陷并取代细胞核。FD 是相分离液体,其界面张力 γ 尚不清楚,它决定了 FD 如何与其他细胞器相互作用。在这里,微米大小的 FD 在压入核周肌动球蛋白和细胞核时保持球形,同时导致独立于 Lamin-A、C 的 Lamin-B1 局部稀释,有时会引发核破裂。细胞质 DNA 传感器 cGAS 在破裂部位的局部积累伴随着 DNA 修复因子持续错误定位到细胞质、DNA 损伤增加和细胞周期延迟。巨噬细胞显示 FD 和吞噬的刚性珠会导致类似的压痕稀释。小 FD 的球形表明具有高 γ,我们对从新鲜脂肪组织中机械分离的 FD 进行测量,其值为 ~40 mN/m。该值远高于蛋白质缩合物的值,但是水中油的典型值,并且刚性足以扰乱包括细胞核在内的细胞结构。
更新日期:2023-05-22
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