Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins
Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins
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DOI：
10.1016/j.cell.2016.05.006
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发表时间：
2016-06-30
期刊：
影响因子：
64.5
通讯作者：
Nystrom, Thomas
中科院分区：
文献类型：
--
作者：
Hanzen, Sarah;Vielfort, Katarina;Nystrom, Thomas
热量限制（CR）通过抵消与年龄相关的H2O2清除过氧化物酶（Prxs）氧化来延长苍蝇，蠕虫和酵母的寿命。在这里，我们表明，增加剂量的主要胞质Prx在酵母，Tsa1，延长寿命的Hsp70分子伴侣依赖和CR独立的方式，而不增加过氧化氢清除或基因组稳定性。我们发现，Tsa1和热休克蛋白70物理相互作用，过氧化氢的Tsa1是所需的招聘的热休克蛋白70分子伴侣和热休克蛋白104解聚酶的错误折叠和聚集的蛋白质在老化，但不是热应激。Tsa1抵消积累的泛素化的聚集体在老化过程中和还原过氧化氢生成的聚集体的清除促进硫化氧还蛋白的过氧化Tsa1。这些数据揭示了一个概念上的新作用，过氧化氢信号在蛋白质和寿命控制和新的光赋予真核生物过氧化物酶的选择性的好处，其可逆的超氧化。
Caloric restriction (CR) extends the lifespan of flies, worms, and yeast by counteracting age-related oxidation of H2O2-scavenging peroxiredoxins (Prxs). Here, we show that increased dosage of the major cytosolic Prx in yeast, Tsa1, extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without increasing H2O2 scavenging or genome stability. We found that Tsa1 and Hsp70 physically interact and that hyperoxidation of Tsa1 by H2O2 is required for the recruitment of the Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not heat stress. Tsa1 counteracted the accumulation of ubiquitinated aggregates during aging and the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates. The data reveal a conceptually new role for H2O2 signaling in proteostasis and lifespan control and shed new light on the selective benefits endowed to eukaryotic peroxiredoxins by their reversible hyperoxidation.