Misfolding-prone proteins are reversibly sequestered to an Hsp42-associated granule upon chronological aging
Misfolding-prone proteins are reversibly sequestered to an Hsp42-associated granule upon chronological aging
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DOI：
10.1242/jcs.220202
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发表时间：
2018-08-01
影响因子：
4
通讯作者：
Leu, Jun-Yi
中科院分区：
文献类型：
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作者：
Lee, Hsin-Yi;Chao, Jung-Chi;Leu, Jun-Yi
蛋白质定位的改变是细胞在环境胁迫下调节蛋白质稳态的重要策略。在萌芽的酿酒酵母中，许多蛋白质在时间老化过程中重新定位并形成胞质颗粒。然而，在大多数情况下，这些蛋白质颗粒的功能和确切成分仍然不清楚。在本研究中，我们对固定相细胞的蛋白定位进行了全基因组分析，发现了307个颗粒形成蛋白，并鉴定了hsp42 -固定相颗粒（Hsp42-SPG）、p小体、Ret2颗粒和肌动蛋白小体中的新组分。我们进一步鉴定了Hsp42-SPG，它含有最多的蛋白质成分，包括许多分子伴侣、代谢酶和调节蛋白。Hsp42-SPG的形成有效地下调了隔离成分的活性，这些成分可以根据环境线索从颗粒中不同地释放出来。我们在全基因组复制前的酵母物种Lachancea kluyveri中发现了类似的结构，这表明Hsp42-SPG是一种常见的机制，允许按时间老化的细胞在可用能量有限的情况下应对不断变化的环境。本文以第一人称采访了该论文的第一作者。
Alteration of protein localization is an important strategy for cells to regulate protein homeostasis upon environmental stresses. In the budding yeast Saccharomyces cerevisiae, many proteins relocalize and form cytosolic granules during chronological aging. However, the functions and exact components of these protein granules remain uncharacterized in most cases. In this study, we performed a genome-wide analysis of protein localization in stationary phase cells, leading to the discovery of 307 granule-forming proteins and the identification of new components in the Hsp42-stationary phase granule (Hsp42-SPG), P-bodies, Ret2 granules and actin bodies. We further characterized the Hsp42-SPG, which contains the largest number of protein components, including many molecular chaperones, metabolic enzymes and regulatory proteins. Formation of the Hsp42-SPG efficiently downregulates the activities of sequestered components, which can be differentially released from the granule based on environmental cues. We found a similar structure in the pre-whole genome duplication yeast species, Lachancea kluyveri, suggesting that the Hsp42-SPG is a common machinery allowing chronologically aged cells to contend with changing environments when available energy is limited.This article has an associated First Person interview with the first author of the paper.