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

Wojciech P. Lipiński, Brent S. Visser, Irina Robu, Mohammad A.A. Fakhree, Saskia Lindhoud, Mireille M.A.E. Claessens, Evan Spruijt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)
124 Downloads (Pure)

Abstract

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 proteins with preexisting condensates that act as localization centers could be a far more general mechanism of altering 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 α-synuclein and two truncated α-synuclein variants 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.

Original languageEnglish
Article numbereabq6495
JournalScience advances
Volume8
Issue number48
DOIs
Publication statusPublished - 2 Dec 2022

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