Biomolecular condensates can both accelerate and suppress aggregation of a-synuclein

Biomolecular condensates present in cells can fundamentally affect the aggregation of amyloidogenic proteins and play a role in the regulation of this process. While liquid-liquid phase separation of amyloidogenic proteins by themselves can act as an alternative nucleation pathway, interaction of partly disordered aggregation-prone pro-teins with preexisting condensates that act as localization centers could be a far more general mechanism of alter-ing their aggregation behavior. Here, we show that so-called host biomolecular condensates can both accelerate and slow down amyloid formation. We study the amyloidogenic protein a-synuclein and two truncated a-synuclein vari-ants in the presence of three types of condensates composed of nonaggregating peptides, RNA, or ATP. Our results demonstrate that condensates can markedly speed up amyloid formation when proteins localize to their interface. However, condensates can also significantly suppress aggregation by sequestering and stabilizing amyloidogenic proteins, thereby providing living cells with a possible protection mechanism against amyloid formation.

Automated summary

Biomolecular condensates in cells can regulate the aggregation behavior of amyloidogenic proteins. They can either accelerate amyloid formation by acting as localization centers or suppress aggregation by sequestering and stabilizing amyloidogenic proteins, providing a possible protection mechanism against amyloid formation in living cells.