法国蔚蓝海岸大学Thomas Bertero等研究人员合作发现，机械依赖性的山梨醇积累支持生物分子凝聚体。2024年11月25日，《细胞》杂志在线发表了这一最新研究成果。
研究人员提供证据表明，基质硬化促进了体内生物分子凝聚的形成。研究人员展示了细胞外基质将机械信号与葡萄糖代谢控制联系起来，进而转化为山梨醇。山梨醇作为天然的拥挤因子，促进了生物分子凝聚。
通过计算机模拟和体外实验，研究人员确定了山梨醇浓度在生理范围内的变化，而非葡萄糖浓度的变化，足以调控生物分子凝聚体。因此，通过药理学和遗传学手段操控细胞内山梨醇浓度，可以调节乳腺癌中的生物分子凝聚体——一种机械依赖性疾病。
研究人员提出山梨醇是一种机械敏感代谢产物，能够促进蛋白质凝聚，进而调控机械调节的细胞功能。
据了解，凝集的蛋白质液滴调节着许多细胞功能，然而调节其形成的生理条件在很大程度上仍未被探索。增加人们对这些机制的理解是至关重要的，因为不能控制凝聚物的形成和动力学可能导致许多疾病。
附：英文原文
Title: Mechano-dependent sorbitol accumulation supports biomolecular condensate
Author: Stephanie Torrino, William M. Oldham, Andrés R. Tejedor, Ignacio S. Burgos, Lara Nasr, Nesrine Rachedi, Kéren Fraissard, Caroline Chauvet, Chaima Sbai, Brendan P. O’Hara, Sophie Abélanet, Frederic Brau, Cyril Favard, Stephan Clavel, Rosana Collepardo-Guevara, Jorge R. Espinosa, Issam Ben-Sahra, Thomas Bertero
Issue&Volume: 2024-11-25
Abstract: Condensed droplets of protein regulate many cellular functions, yet the physiological conditions regulating their formation remain largely unexplored. Increasing our understanding of these mechanisms is paramount, as failure to control condensate formation and dynamics can lead to many diseases. Here, we provide evidence that matrix stiffening promotes biomolecular condensation in vivo. We demonstrate that the extracellular matrix links mechanical cues with the control of glucose metabolism to sorbitol. In turn, sorbitol acts as a natural crowding agent to promote biomolecular condensation. Using in silico simulations and in vitro assays, we establish that variations in the physiological range of sorbitol concentrations, but not glucose concentrations, are sufficient to regulate biomolecular condensates. Accordingly, pharmacological and genetic manipulation of intracellular sorbitol concentration modulates biomolecular condensates in breast cancer—a mechano-dependent disease. We propose that sorbitol is a mechanosensitive metabolite enabling protein condensation to control mechano-regulated cellular functions.
DOI: 10.1016/j.cell.2024.10.048
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01271-6