Protein aggregates are formed in cells with profoundly perturbed proteostasis, where the generation of misfolded proteins exceeds the cellular refolding and degradative capacity. They are a hallmark of protein conformational disorders and aged and/or environmentally stressed cells. Protein aggregation is a reversible process in vivo, which counteracts proteotoxicities derived from aggregate persistence, but the chaperone machineries involved in protein disaggregation in Metazoa were uncovered only recently. Here we highlight recent advances in the mechanistic understanding of the major protein disaggregation machinery mediated by the Hsp70 chaperone system and discuss emerging alternative disaggregation activities in multicellular organisms.

蛋白聚集体是在蛋白紊乱严重的细胞中形成的，错折叠蛋白的产生超过了细胞的复性和降解能力。它们是蛋白质构象障碍以及老化和/或受环境压力的细胞的标志。蛋白质聚集是体内可逆的过程，可抵消源自聚集持久性的蛋白毒性，但直到最近才发现与后生动物蛋白质分解有关的分子伴侣机制。在这里，我们重点介绍由Hsp70分子伴侣系统介导的主要蛋白质分解机制的机械理解的最新进展，并讨论了在多细胞生物中新兴的替代分解活性。