Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.

Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.
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DOI:
10.1111/acel.12032
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发表时间:
2013-02
期刊:
影响因子:
7.8
通讯作者:
Kaeberlein M
Kaeberlein M
中科院分区:
生物学1区
文献类型:
--
作者:
Delaney JR;Ahmed U;Chou A;Sim S;Carr D;Murakami CJ;Schleit J;Sutphin GL;An EH;Castanza A;Fletcher M;Higgins S;Jelic M;Klum S;Muller B;Peng ZJ;Rai D;Ros V;Singh M;Wende HV;Kennedy BK;Kaeberlein M

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虽然环境压力可能在促进衰老方面起着重要作用,但这种关系仍然知之甚少。为了以更全面的方式表征这种相互作用,我们研究了46种长寿酵母突变株在四种不同应激条件(氧化,ER,DNA损伤和热)下的应激反应谱,根据其相关的应激反应谱对基因进行分组。出乎意料的是,缺乏线粒体AAA蛋白酶基因AFG3的细胞与缺乏大亚基的胞质核糖体蛋白的长寿菌株强烈聚类。与这些核糖体蛋白突变体类似,afg3Δ细胞显示出细胞质mRNA翻译减少,对衣霉素的抗性增强,这与ER未折叠蛋白反应无关,并且Sir2不依赖但Gcn 4依赖的寿命延长。这些数据证明了线粒体蛋白酶、细胞质mRNA翻译和衰老之间的意外联系。
While environmental stress likely plays a significant role in promoting aging, the relationship remains poorly understood. In order to characterize this interaction in a more comprehensive manner, we examined the stress response profiles for 46 long-lived yeast mutant strains across four different stress conditions (oxidative, ER, DNA damage, and thermal), grouping genes based on their associated stress response profiles. Unexpectedly, cells lacking the mitochondrial AAA protease gene AFG3 clustered strongly with long-lived strains lacking cytosolic ribosomal proteins of the large subunit. Similar to these ribosomal protein mutants, afg3Δ cells show reduced cytoplasmic mRNA translation, enhanced resistance to tunicamycin that is independent of the ER unfolded protein response, and Sir2-independent but Gcn4-dependent life span extension. These data demonstrate an unexpected link between a mitochondrial protease, cytoplasmic mRNA translation, and aging.
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