Calorie Restriction Reduces Oxidative Stress by SIRT3-Mediated SOD2 Activation
Calorie Restriction Reduces Oxidative Stress by SIRT3-Mediated SOD2 Activation
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DOI：
10.1016/j.cmet.2010.11.015
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发表时间：
2010-12-01
期刊：
影响因子：
29
通讯作者：
Chen, Danica
中科院分区：
文献类型：
--
作者：
Qiu, Xiaolei;Brown, Katharine;Chen, Danica
衰老和许多疾病的一个主要原因被认为是累积的氧化应激，由呼吸过程中产生的活性氧（ROS）引起。热量限制（CR）是延长哺乳动物寿命和改善各种疾病的最有力的干预措施，可减少氧化应激和损伤。然而，其潜在机制尚不清楚。在这里，我们发现CR对氧化应激和损伤的保护作用在缺乏SIRT3（一种线粒体脱乙酰酶）的小鼠中减弱。SIRT3依赖于超氧化物歧化酶2（SOD 2）降低细胞ROS水平，SOD 2是一种主要的线粒体抗氧化酶。SIRT3使SOD 2上的两个关键赖氨酸残基脱乙酰化，并促进其抗氧化活性。重要的是，SOD2减少细胞ROS和促进氧化应激抗性的能力被SIRT3大大增强。我们的研究确定了一个防御计划，CR挑起减少氧化应激，并提出了对抗衰老和氧化应激相关疾病的方法。
A major cause of aging and numerous diseases is thought to be cumulative oxidative stress, resulting from the production of reactive oxygen species (ROS) during respiration. Calorie restriction (CR), the most robust intervention to extend life span and ameliorate various diseases in mammals, reduces oxidative stress and damage. However, the underlying mechanism is unknown. Here, we show that the protective effects of CR on oxidative stress and damage are diminished in mice lacking SIRT3, a mitochondrial deacetylase. SIRT3 reduces cellular ROS levels dependent on superoxide dismutase 2 (SOD2), a major mitochondrial antioxidant enzyme. SIRT3 deacetylates two critical lysine residues on SOD2 and promotes its antioxidative activity. Importantly, the ability of SOD2 to reduce cellular ROS and promote oxidative stress resistance is greatly enhanced by SIRT3. Our studies identify a defense program that CR provokes to reduce oxidative stress and suggest approaches to combat aging and oxidative stress-related diseases.