Proteins and RNA can phase separate from the aqueous cellular environment to form subcellular compartments called condensates. This process results in a protein–RNA mixture that is chemically different from the surrounding aqueous phase. Here, we use mass spectrometry to characterize the metabolomes of condensates. To test this, we prepared mixtures of phase-separated proteins and extracts of cellular metabolites and identified metabolites enriched in the condensate phase. Among the most condensate-enriched metabolites were phospholipids, due primarily to the hydrophobicity of their fatty acyl moieties. We found that phospholipids can alter the number and size of phase-separated condensates and in some cases alter their morphology. Finally, we found that phospholipids partition into a diverse set of endogenous condensates as well as artificial condensates expressed in cells. Overall, these data show that many condensates are protein–RNA–lipid mixtures with chemical microenvironments that are ideally suited to facilitate phospholipid biology and signaling.

蛋白质和 RNA 可以从水性细胞环境中相分离，形成称为冷凝物的亚细胞区室。这个过程产生了一种与周围水相化学性质不同的蛋白质-RNA 混合物。在这里，我们使用质谱来表征冷凝物的代谢组。为了测试这一点，我们制备了相分离蛋白质和细胞代谢物提取物的混合物，并鉴定了浓缩相中富集的代谢物。其中最富含冷凝物的代谢物是磷脂，这主要是由于其脂肪酰基部分的疏水性。我们发现磷脂可以改变相分离凝聚物的数量和尺寸，并且在某些情况下改变它们的形态。最后，我们发现磷脂分为多种内源性缩合物以及在细胞中表达的人工缩合物。总的来说，这些数据表明许多缩合物是蛋白质-RNA-脂质混合物，其化学微环境非常适合促进磷脂生物学和信号传导。