Identification of potential calorie restriction-mimicking yeast mutants with increased mitochondrial respiratory chain and nitric oxide levels.
Identification of potential calorie restriction-mimicking yeast mutants with increased mitochondrial respiratory chain and nitric oxide levels.
复制标题
DOI：
10.4061/2011/673185
复制
发表时间：
2011-03-31
影响因子：
4.7
通讯作者：
Lin SJ
中科院分区：
文献类型：
--
作者：
Li B;Skinner C;Castello PR;Kato M;Easlon E;Xie L;Li T;Lu SP;Wang C;Tsang F;Poyton RO;Lin SJ
卡路里限制(CR)诱导代谢向线粒体呼吸转变；然而，CR背后的分子机制尚不清楚。最近的研究表明，CR诱导的线粒体活动与一氧化氮(NO)的产生有关。为了了解线粒体在CR中的作用，我们鉴定和研究了NO水平升高的酿酒酵母突变株作为潜在的CR模拟物。对前17个突变的分析表明，NO增加、线粒体呼吸和寿命之间存在相关性。有趣的是，处理没有供体的酵母，如GSNO(S-亚硝基谷胱甘肽)，足以部分模仿CR来延长寿命。Cr增加的NO在很大程度上依赖于线粒体的电子传递和细胞色素c氧化酶(COX)。虽然COX通常在低氧条件下产生NO，但经CR处理的酵母细胞在常氧条件下能够产生NO。我们的结果表明，CR可能解除了线粒体蛋白的一些低氧基因的表达，这些基因具有促进NO产生和延长寿命的功能。
Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and study Saccharomyces cerevisiae mutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. CR-increased NO is largely dependent on mitochondrial electron transport and cytochrome c oxidase (COX). Although COX normally produces NO under hypoxic conditions, CR-treated yeast cells are able to produce NO under normoxic conditions. Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan.