PMT1 deficiency enhances basal UPR activity and extends replicative lifespan of Saccharomyces cerevisiae.
PMT1 deficiency enhances basal UPR activity and extends replicative lifespan of Saccharomyces cerevisiae.
复制标题
PMT1 缺陷会增强基础 UPR 活性并延长酿酒酵母的复制寿命。
DOI：
10.1007/s11357-015-9788-7
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发表时间：
2015-06-01
期刊：
影响因子：
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通讯作者：
Feng, Wen-Li
中科院分区：
文献类型：
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作者：
Cui, Hong-Jing;Liu, Xin-Guang;Feng, Wen-Li
Pmt 1 p是蛋白质O-甘露糖基转移酶（PMT）家族的重要成员，参与内质网（ER）未折叠蛋白反应（UPR），这是缓解ER应激的重要途径。ER应激和UPR与多种生物体的衰老和年龄相关疾病有关;然而，PMT 1在决定寿命方面的可能作用尚未被描述。在这项研究中，我们报告说，删除PMT 1增加复制寿命（RLS）在芽殖酵母酿酒酵母，而PMT 1（PMT 1-OX）的过表达减少RLS。相对于野生型和PMT 1-OX菌株，pmt 1Delta菌株具有增强的HAC 1 mRNA剪接和升高的UPR靶基因表达水平。此外，增加的RLS的pmt 1Delta菌株可以完全消除删除IRE 1或HAC 1，两个上游调节的UPR。双缺失菌株pmt 1Deltahac 1Delta和pmt 1Deltare 1Delta也显示普遍降低的UPR靶基因转录。总的来说，我们的研究结果表明，PMT 1缺乏增强ER UPR的基础活性，并通过需要IRE 1和HAC 1的机制延长酵母母细胞的RLS。
Pmt1p is an important member of the protein O-mannosyltransferase (PMT) family of enzymes, which participates in the endoplasmic reticulum (ER) unfolded protein response (UPR), an important pathway for alleviating ER stress. ER stress and the UPR have been implicated in aging and age-related diseases in several organisms; however, a possible role for PMT1 in determining lifespan has not been previously described. In this study, we report that deletion of PMT1 increases replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae, while overexpression of PMT1 (PMT1-OX) reduces RLS. Relative to wild-type and PMT1-OX strains, the pmt1Delta strain had enhanced HAC1 mRNA splicing and elevated expression levels of UPR target genes. Furthermore, the increased RLS of the pmt1Delta strain could be completely abolished by deletion of either IRE1 or HAC1, two upstream modulators of the UPR. The double deletion strains pmt1Deltahac1Delta and pmt1Deltaire1Delta also displayed generally reduced transcription of UPR target genes. Collectively, our results suggest that PMT1 deficiency enhances basal activity of the ER UPR and extends the RLS of yeast mother cells through a mechanism that requires both IRE1 and HAC1.