Saarikangas Juha, Barral Yves
Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland.
Elife. 2015 Nov 6;4:e06197. doi: 10.7554/eLife.06197.
Differentiation of cellular lineages is facilitated by asymmetric segregation of fate determinants between dividing cells. In budding yeast, various aging factors segregate to the aging (mother)-lineage, with poorly understood consequences. In this study, we show that yeast mother cells form a protein aggregate during early replicative aging that is maintained as a single, asymmetrically inherited deposit over the remaining lifespan. Surprisingly, deposit formation was not associated with stress or general decline in proteostasis. Rather, the deposit-containing cells displayed enhanced degradation of cytosolic proteasome substrates and unimpaired clearance of stress-induced protein aggregates. Deposit formation was dependent on Hsp42, which collected non-random client proteins of the Hsp104/Hsp70-refolding machinery, including the prion Sup35. Importantly, loss of Hsp42 resulted in symmetric inheritance of its constituents and prolonged the lifespan of the mother cell. Together, these data suggest that protein aggregation is an early aging-associated differentiation event in yeast, having a two-faceted role in organismal fitness.
细胞谱系的分化是由命运决定因子在分裂细胞之间的不对称分离所促进的。在芽殖酵母中，各种衰老因子会分离到衰老的（母本）谱系中，其后果尚不清楚。在这项研究中，我们表明酵母母细胞在早期复制性衰老过程中形成一种蛋白质聚集体，该聚集体在其剩余寿命期间作为单个不对称遗传沉积物得以维持。令人惊讶的是，沉积物的形成与应激或蛋白质稳态的普遍下降无关。相反，含有沉积物的细胞显示出胞质蛋白酶体底物的降解增强，并且对应激诱导的蛋白质聚集体的清除未受损害。沉积物的形成依赖于Hsp42，Hsp42收集了Hsp104/Hsp70重折叠机制的非随机客户蛋白，包括朊病毒Sup35。重要的是，Hsp42的缺失导致其成分的对称遗传，并延长了母细胞的寿命。总之，这些数据表明蛋白质聚集是酵母中与衰老相关的早期分化事件，在生物体适应性方面具有双重作用。
