Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins
Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins
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DOI：
10.1096/fj.05-5568com
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发表时间：
2006-06-01
期刊：
影响因子：
4.8
通讯作者：
Barja, Gustavo
中科院分区：
文献类型：
--
作者：
Sanz, Alberto;Caro, Pilar;Barja, Gustavo
先前的研究一致表明，热量限制（CR）减少线粒体活性氧（ROS）（mitROS）的产生和对线粒体DNA和线粒体蛋白的氧化损伤，并增加最长寿命，尽管对此负责的机制尚不清楚。我们最近发现，蛋白质限制（PR）也产生这些变化独立于能量限制。各种事实将甲硫氨酸与衰老联系起来，并且甲硫氨酸限制（MetR）没有能量限制，像CR一样，最长寿命增加。因此，我们假设MetR是PR和CR中mitROS生成和氧化应激减少的原因。在这项研究中，我们对雄性大鼠进行了完全相同的MetR饮食方案，这是已知的，可以增加它们的寿命。我们第一次发现，MetR显著降低了mitROS的产生，减少了对mtDNA的氧化损伤，降低了膜不饱和度，并降低了大鼠心脏和肝脏线粒体中测量的所有五种蛋白质氧化标志物。络合物I和IV的浓度也在MetR中降低。线粒体生成的减少发生在肝脏中的复合物I和III中以及心脏线粒体中的复合物I中，并且是由于呼吸链在避免电子泄漏到氧气中的效率增加。这些变化与CR和PR中观察到的变化惊人地相似，表明蛋氨酸摄入的减少是线粒体ROS产生和氧化应激减少的原因，并且可能是热量限制期间发生的衰老率降低的一部分。
Previous studies have consistently shown that caloric restriction (CR) decreases mitochondrial reactive oxygen species (ROS) (mitROS) generation and oxidative damage to mtDNA and mitochondrial proteins, and increases maximum longevity, although the mechanisms responsible for this are unknown. We recently found that protein restriction ( PR) also produces these changes independent of energy restriction. Various facts link methionine to aging, and methionine restriction (MetR) without energy restriction increases, like CR, maximum longevity. We have thus hypothesized that MetR is responsible for the decrease in mitROS generation and oxidative stress in PR and CR. In this investigation we subjected male rats to exactly the same dietary protocol of MetR that is known to increase their longevity. We have found, for the first time, that MetR profoundly decreases mitROS production, decreases oxidative damage to mtDNA, lowers membrane unsaturation, and decreases all five markers of protein oxidation measured in rat heart and liver mitochondria. The concentration of complexes I and IV also decreases in MetR. The decrease in mitROS generation occurs in complexes I and III in liver and in complex I in heart mitochondria, and is due to an increase in efficiency of the respiratory chain in avoiding electron leak to oxygen. These changes are strikingly similar to those observed in CR and PR, suggesting that the decrease in methionine ingestion is responsible for the decrease in mitochondrial ROS production and oxidative stress, and possibly part of the decrease in aging rate, occurring during caloric restriction.