Proteomic analysis of dietary restriction in yeast reveals a role for Hsp26 in replicative lifespan extension.
Proteomic analysis of dietary restriction in yeast reveals a role for Hsp26 in replicative lifespan extension.
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DOI：
10.1042/bcj20210432
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发表时间：
2021-12-22
期刊：
影响因子：
--
通讯作者：
Morgan A
中科院分区：
文献类型：
--
作者：
Campion R;Bloxam L;Burrow K;Brownridge PJ;Pentland DR;Thomas P;Gourlay CW;Eyers CE;Barclay JW;Morgan A
饮食限制（DR）已被证明可以延长从酵母到哺乳动物等生物体的寿命。这表明潜在的机制可能在进化上是保守的。事实上，上游信号通路（例如 TOR）与 DR 诱导的各种生物体的寿命密切相关。然而，最终介导寿命延长的下游效应蛋白尚不清楚。为了阐明这一点，我们对芽殖酵母使用了蛋白质组学方法。我们的理由是，对 DR 引起的整个蛋白质组变化的分析可能能够识别介导其生理效应（包括复制寿命延长）的蛋白质。在我们通过液相色谱-质谱法鉴定的 2500 多种蛋白质中，有 183 种蛋白质的表达因 DR 的影响而显着改变至少 3 倍。这些蛋白质大多数是线粒体的和/或与呼吸和新陈代谢有明确的联系。事实上，对耗氧量的直接分析证实，线粒体呼吸因 DR 的作用而增加了数倍。此外，DR 下调了参与交配的几种关键蛋白，包括 Ste2 和 Ste6。与此相一致的是，DR 减少了响应 α 因子信息素的 shmoo 形成，从而证实了 DR 对酵母交配的抑制作用。最后，我们发现 Hsp26（保守的小热休克蛋白（sHSP）家族的成员）被 DR 上调，并且 Hsp26 的过度表达延长了酵母的复制寿命。由于 sHSP 在秀丽隐杆线虫和果蝇中的过度表达先前已被证明可以延长寿命，因此我们关于酵母 Hsp26 的数据表明 sHSP 可能是普遍保守的长寿效应子。
Dietary restriction (DR) has been shown to increase lifespan in organisms ranging from yeast to mammals. This suggests that the underlying mechanisms may be evolutionarily conserved. Indeed, upstream signalling pathways, such as TOR, are strongly linked to DR-induced longevity in various organisms. However, the downstream effector proteins that ultimately mediate lifespan extension are less clear. To shed light on this, we used a proteomic approach on budding yeast. Our reasoning was that analysis of proteome-wide changes in response to DR might enable the identification of proteins that mediate its physiological effects, including replicative lifespan extension. Of over 2500 proteins we identified by liquid chromatography–mass spectrometry, 183 were significantly altered in expression by at least 3-fold in response to DR. Most of these proteins were mitochondrial and/or had clear links to respiration and metabolism. Indeed, direct analysis of oxygen consumption confirmed that mitochondrial respiration was increased several-fold in response to DR. In addition, several key proteins involved in mating, including Ste2 and Ste6, were down-regulated by DR. Consistent with this, shmoo formation in response to α-factor pheromone was reduced by DR, thus confirming the inhibitory effect of DR on yeast mating. Finally, we found that Hsp26, a member of the conserved small heat shock protein (sHSP) family, was up-regulated by DR and that overexpression of Hsp26 extended yeast replicative lifespan. As overexpression of sHSPs in Caenorhabditis elegans and Drosophila has previously been shown to extend lifespan, our data on yeast Hsp26 suggest that sHSPs may be universally conserved effectors of longevity.
影响因子：
7.8
作者：
Smith DL Jr;Li C;Matecic M;Maqani N;Bryk M;Smith JS
通讯作者：
Smith JS
影响因子：
7.8
作者：
Riesen M;Morgan A
通讯作者：
Morgan A