Membrane contact between intracellular organelles is important in mediating organelle communication. However, the assembly of molecular machinery at membrane contact site and its internal organization correlating with its functional activity remain unclear. Here, we demonstrate that a gel-like condensation of Cidec, a crucial protein for obesity development by facilitating lipid droplet (LD) fusion, occurs at the LD-LD contact site (LDCS) through phase separation. The homomeric interaction between the multivalent N terminus of Cidec is sufficient to promote its phase separation both in vivo and in vitro. Interestingly, Cidec condensation at LDCSs generates highly plastic and lipid-permeable fusion plates that are geometrically constrained by donor LDs. In addition, Cidec condensates are distributed unevenly in the fusion plate generating stochastic sub-compartments that may represent unique lipid passageways during LD fusion. We have thus uncovered the organization and functional significance of geometry-constrained Cidec phase separation in mediating LD fusion and lipid homeostasis.

细胞内细胞器之间的膜接触在介导细胞器通讯中很重要。然而，膜接触位点的分子机器组装及其与其功能活动相关的内部组织仍不清楚。在这里，我们证明了 Cidec 的凝胶状缩合，Cidec 是一种通过促进脂滴 (LD) 融合促进肥胖发展的关键蛋白质，通过相分离发生在 LD-LD 接触位点 (LDCS)。Cidec 多价 N 末端之间的同聚相互作用足以促进其在体内和体外的相分离. 有趣的是，LDCS 上的 Cidec 冷凝产生了高度可塑性和脂质渗透性的融合板，这些融合板在几何上受到供体 LD 的限制。此外，Cidec 冷凝物在融合板中分布不均匀，产生随机子隔室，可能代表 LD 融合过程中独特的脂质通道。因此，我们揭示了几何约束的 Cidec 相分离在介导 LD 融合和脂质稳态方面的组织和功能意义。