Oxidative stress conditions increase the frequency of de novo formation of the yeast [PSI+] prion.
Oxidative stress conditions increase the frequency of de novo formation of the yeast [PSI+] prion.
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DOI：
10.1111/mmi.12930
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发表时间：
2015-04
影响因子：
3.6
通讯作者：
Grant CM
中科院分区：
文献类型：
--
作者：
Doronina VA;Staniforth GL;Speldewinde SH;Tuite MF;Grant CM
朊病毒是一种自我维持的淀粉样蛋白聚集体，是哺乳动物各种神经退行性疾病和酵母遗传特征的基础。酵母和哺乳动物朊病毒如何自发形成感染性淀粉样结构的分子基础知之甚少。我们已经探讨了假设，氧化应激是一个通用的触发朊病毒形成的酵母[PSI +]朊病毒，这是改变构象的Sup 35翻译终止因子。我们发现，[PSI +]朊病毒形成的频率升高的条件下的氧化应激和突变体缺乏关键的抗氧化剂。我们检测到增加氧化的Sup 35蛋氨酸残基的抗氧化剂突变体，并表明蛋氨酸亚砜还原酶的过度表达废除了氧化Sup 35和它的转换为[PSI +]朊病毒。[PSI+]朊病毒形成在缺乏Sod 1 Cu，Zn-超氧化物歧化酶的突变体中特别升高。我们已经使用荧光显微镜显示，从头出现的[PSI +]是快速和增加的频率在这个突变体。最后，天然Sup 35的电子显微镜分析显示，在野生型和抗氧化剂突变体中形成了类似的纤维状结构。总之，我们的数据表明，氧化应激是[PSI +]形成的一般触发因素，可以通过抗氧化防御来缓解。
Prions are self‐perpetuating amyloid protein aggregates which underlie various neurodegenerative diseases in mammals and heritable traits in yeast. The molecular basis of how yeast and mammalian prions form spontaneously into infectious amyloid‐like structures is poorly understood. We have explored the hypothesis that oxidative stress is a general trigger for prion formation using the yeast [PSI +] prion, which is the altered conformation of the Sup35 translation termination factor. We show that the frequency of [PSI +] prion formation is elevated under conditions of oxidative stress and in mutants lacking key antioxidants. We detect increased oxidation of Sup35 methionine residues in antioxidant mutants and show that overexpression of methionine sulphoxide reductase abrogates both the oxidation of Sup35 and its conversion to the [PSI +] prion. [PSI +] prion formation is particularly elevated in a mutant lacking the Sod1 Cu,Zn‐superoxide dismutase. We have used fluorescence microscopy to show that the de novo appearance of [PSI +] is both rapid and increased in frequency in this mutant. Finally, electron microscopy analysis of native Sup35 reveals that similar fibrillar structures are formed in both the wild‐type and antioxidant mutants. Together, our data indicate that oxidative stress is a general trigger of [PSI +] formation, which can be alleviated by antioxidant defenses.
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影响因子：
3.6
作者：
Garrido, EO;Grant, CM
通讯作者：
Grant, CM
DOI：
10.1111/j.1532-5415.1972.tb00787.x
发表时间：
1972-01-01
影响因子：
6.3
作者：
HARMAN, D
通讯作者：
HARMAN, D
DOI：
10.3109/10715769309111598
发表时间：
1993-01-01
期刊：
FREE RADICAL RESEARCH COMMUNICATIONS
影响因子：
--
作者：
GUTTERIDGE, JMC
通讯作者：
GUTTERIDGE, JMC
影响因子：
5.3
作者：
Ganusova, EE;Ozolins, LN;Chernoff, YO
通讯作者：
Chernoff, YO
影响因子：
64.8
作者：
King, CY;Diaz-Avalos, R
通讯作者：
Diaz-Avalos, R