SOD2 functions downstream of Sch9 to extend longevity in yeast.

SOD2 functions downstream of Sch9 to extend longevity in yeast.
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SOD2 在 Sch9 下游发挥作用,可延长酵母的寿命。

DOI:
10.1093/genetics/163.1.35
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发表时间:
2003
期刊:
影响因子:
3.3
通讯作者:
Longo,ValterD
Longo,ValterD
中科院分区:
生物学2区
文献类型:
--
作者:
Fabrizio,Paola;Liou,Lee-Loung;Moy,VanessaN;Diaspro,Alberto;Valentine,JoanSelverstone;Gralla,EdithButler;Longo,ValterD

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饥饿期间失活的信号转导通路与调节从酵母到哺乳动物的各种生物的寿命有关,但对延长寿命的机制知之甚少。按时间顺序延长寿命的INS。酿酒酵母cyr1和sch9突变体是由抗逆境蛋白MSN2/MSN4和Rim15介导的。在这里,我们证明了线粒体超氧化物歧化酶(Sod2)是酵母中生存延长所必需的。SOD2的缺失取消了Δ突变体的寿命延长,并降低了cyr1:mTn突变体的存活率。超氧化物歧化酶-线粒体Sod2和胞质CuZnSod(SOD1)-的过表达延迟了线粒体乌头酸酶的年龄依赖性可逆失活,并延长了30%的存活率。RAS2基因的缺失也会使人的平均寿命翻倍,这是一种需要MSN2/4和Sod2的机制。RAS2基因位于Cyr1上游。这些发现与延长INS的实际寿命的突变有关。这一结果表明,酿酒人最大限度地延长寿命需要诱导其他受MSN2/4和Rim15调控的抗逆基因。
Signal transduction pathways inactivated during periods of starvation are implicated in the regulation of longevity in organisms ranging from yeast to mammals, but the mechanisms responsible for life-span extension are poorly understood. Chronological life-span extension inS. cerevisiae cyr1andsch9mutants is mediated by the stress-resistance proteins Msn2/Msn4 and Rim15. Here we show that mitochondrial superoxide dismutase (Sod2) is required for survival extension in yeast. Deletion ofSOD2abolishes life-span extension insch9Δ mutants and decreases survival incyr1:mTnmutants. The overexpression of Sods—mitochondrial Sod2 and cytosolic CuZnSod (Sod1)—delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends survival by 30%. Deletion of theRAS2gene, which functions upstream ofCYR1, also doubles the mean life span by a mechanism that requires Msn2/4 and Sod2. These findings link mutations that extend chronological life span inS. cerevisiaeto superoxide dismutases and suggest that the induction of other stress-resistance genes regulated by Msn2/4 and Rim15 is required for maximum longevity extension.
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