A role for the actin cytoskeleton in cell death and aging in yeast.
A role for the actin cytoskeleton in cell death and aging in yeast.
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DOI：
10.1083/jcb.200310148
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发表时间：
2004-03-15
期刊：
影响因子：
--
通讯作者：
Ayscough KR
中科院分区：
文献类型：
--
作者：
Gourlay CW;Carpp LN;Timpson P;Winder SJ;Ayscough KR
衰老的几个决定因素，包括代谢能力和遗传稳定性，在酵母和人类中都是公认的。然而，导致细胞死亡的途径的许多方面仍有待阐明。在这里，我们报告了肌动蛋白细胞骨架在细胞死亡和促进寿命方面的作用。我们分析了表达突变的酵母菌株与肌动蛋白动力学增加或减少。我们发现肌动蛋白动力学降低导致线粒体膜去极化和活性氧（ROS）产生增加，导致细胞死亡。然而，重要的是，通过特定的肌动蛋白等位基因或通过删除编码肌动蛋白捆绑蛋白Scp1p的基因来增加肌动蛋白动力学，可以使寿命延长65%以上。延长寿命似乎是由于这些细胞产生的ROS水平低于野生型。Scp1p与哺乳动物SM22/transgelin之间的同源性表明，衰老与肌动蛋白稳定性之间存在保守的联系机制。
Several determinants of aging, including metabolic capacity and genetic stability, are recognized in both yeast and humans. However, many aspects of the pathways leading to cell death remain to be elucidated. Here we report a role for the actin cytoskeleton both in cell death and in promoting longevity. We have analyzed yeast strains expressing mutants with either increased or decreased actin dynamics. We show that decreased actin dynamics causes depolarization of the mitochondrial membrane and an increase in reactive oxygen species (ROS) production, resulting in cell death. Important, however, is the demonstration that increasing actin dynamics, either by a specific actin allele or by deletion of a gene encoding the actin-bundling protein Scp1p, can increase lifespan by over 65%. Increased longevity appears to be due to these cells producing lower than wild-type levels of ROS. Homology between Scp1p and mammalian SM22/transgelin, which itself has been isolated in senescence screens, suggests a conserved mechanism linking aging to actin stability.
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