Department of Pharmacology, Weill Cornell Medical College, Cornell University, New York, NY, USA.
Nat Chem Biol. 2024 Mar;20(3):302-313. doi: 10.1038/s41589-023-01474-4. Epub 2023 Nov 16.
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 可以从细胞的水性环境中相分离，形成称为凝聚物的亚细胞隔室。这个过程导致蛋白质-RNA 的混合物在化学上与周围的水性相不同。在这里，我们使用质谱法来描述凝聚物的代谢组。为了验证这一点，我们制备了相分离蛋白质和细胞代谢物提取物的混合物，并鉴定了在凝聚物相中富集的代谢物。在最富含凝聚物的代谢物中，由于其脂肪酸部分的疏水性，主要是磷脂。我们发现磷脂可以改变相分离凝聚物的数量和大小，并在某些情况下改变它们的形态。最后，我们发现磷脂分配到多种内源性凝聚物以及细胞中表达的人工凝聚物中。总的来说，这些数据表明，许多凝聚物是蛋白质-RNA-脂质混合物，具有化学微环境，非常适合促进磷脂生物学和信号转导。
