Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae
Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m408918200
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发表时间：
2004-11-26
影响因子：
4.8
通讯作者：
Kowaltowski, AJ
中科院分区：
文献类型：
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作者：
Barros, MH;Bandy, B;Kowaltowski, AJ
由于热量限制，酿酒酵母复制寿命的延长与线粒体呼吸活性的增强有关。在这里，我们进一步研究了线粒体呼吸如何影响酵母寿命。我们发现，低葡萄糖条件下生长所限制的热量增加了呼吸作用，但相对于耗氧量而言，线粒体活性氧的产生却减少了。热量限制也延长了实际寿命。热量限制对线粒体呼吸、活性氧释放以及复制寿命和时间寿命的有益影响可以通过二硝基苯酚等解偶联剂来模拟。相反，用抗霉素（强烈增加线粒体活性氧生成）处理的细胞或线粒体超氧化物歧化酶（去除超氧自由基）和RTG2（参与线粒体和细胞核之间的逆行反馈信号）无效的酵母突变体中，按时间顺序的寿命缩短。这些结果表明，酵母衰老与线粒体代谢和氧化应激的变化有关，并且轻微的线粒体解偶联可以延长时间寿命和复制寿命。
Increased replicative longevity in Saccharomyces cerevisiae because of calorie restriction has been linked to enhanced mitochondrial respiratory activity. Here we have further investigated how mitochondrial respiration affects yeast life span. We found that calorie restriction by growth in low glucose increased respiration but decreased mitochondrial reactive oxygen species production relative to oxygen consumption. Calorie restriction also enhanced chronological life span. The beneficial effects of calorie restriction on mitochondrial respiration, reactive oxygen species release, and replicative and chronological life span could be mimicked by uncoupling agents such as dinitrophenol. Conversely, chronological life span decreased in cells treated with antimycin (which strongly increases mitochondrial reactive oxygen species generation) or in yeast mutants null for mitochondrial superoxide dismutase (which removes superoxide radicals) and for RTG2 (which participates in retrograde feedback signaling between mitochondria and the nucleus). These results suggest that yeast aging is linked to changes in mitochondrial metabolism and oxidative stress and that mild mitochondrial uncoupling can increase both chronological and replicative life span.