Tor1 regulates protein solubility in Saccharomyces cerevisiae.
Tor1 regulates protein solubility in Saccharomyces cerevisiae.
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DOI：
10.1091/mbc.e12-08-0620
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发表时间：
2012-12
影响因子：
3.3
通讯作者：
Hughes RE
中科院分区：
文献类型：
--
作者：
Peters TW;Rardin MJ;Czerwieniec G;Evani US;Reis-Rodrigues P;Lithgow GJ;Mooney SD;Gibson BW;Hughes RE
靶向自噬降解的蛋白质从可溶性阶段向不溶性阶段的转变是由TORC1以一种不依赖于atg1的机制调节的。这一过程可能是蛋白质组学应激时维持蛋白质稳态的关键机制。细胞中不溶性蛋白的积累与衰老和衰老相关疾病有关；然而，不溶性蛋白在这些过程中的作用是不确定的。正常衰老过程中蛋白质溶解度变化的性质和影响尚不清楚。利用定量质谱法，我们鉴定了酿酒酵母在有丝分裂后衰老过程中变得不溶性的480种蛋白质，并表明这种不溶性蛋白质的集合与衰老线虫中积累的蛋白质相似。sds不溶性蛋白仅存在于有丝分裂后细胞的非静止亚群中，表明该蛋白的分布不对称。此外，我们发现年轻细胞的氮饥饿足以引起类似的一组不溶性蛋白质的积累。虽然许多已鉴定的不溶性蛋白是已知的自噬底物，但不溶性蛋白的形成并不需要诱导大自噬。然而，遗传或化学抑制Tor1激酶足以促进不溶性蛋白的积累。我们得出结论，雷帕霉素复合物1的靶标通过作用于巨噬上游的机制调节不溶性蛋白的积累。我们的数据表明，有丝分裂后细胞中以sds不溶状态积累的蛋白质代表了一种由Tor1激酶调节的新型自噬货物制备过程。
The transition of proteins targeted for autophagic degradation from the soluble to the insoluble phase is regulated in an ATG1-independent mechanism by TORC1. This process is likely a critical mechanism for maintaining protein homeostasis when challenged with proteomic stress. Accumulation of insoluble protein in cells is associated with aging and aging-related diseases; however, the roles of insoluble protein in these processes are uncertain. The nature and impact of changes to protein solubility during normal aging are less well understood. Using quantitative mass spectrometry, we identify 480 proteins that become insoluble during postmitotic aging in Saccharomyces cerevisiae and show that this ensemble of insoluble proteins is similar to those that accumulate in aging nematodes. SDS-insoluble protein is present exclusively in a nonquiescent subpopulation of postmitotic cells, indicating an asymmetrical distribution of this protein. In addition, we show that nitrogen starvation of young cells is sufficient to cause accumulation of a similar group of insoluble proteins. Although many of the insoluble proteins identified are known to be autophagic substrates, induction of macroautophagy is not required for insoluble protein formation. However, genetic or chemical inhibition of the Tor1 kinase is sufficient to promote accumulation of insoluble protein. We conclude that target of rapamycin complex 1 regulates accumulation of insoluble proteins via mechanisms acting upstream of macroautophagy. Our data indicate that the accumulation of proteins in an SDS-insoluble state in postmitotic cells represents a novel autophagic cargo preparation process that is regulated by the Tor1 kinase.