Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction.
Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction.
复制标题
SIRT3在饮食限制期间促进尿素周期和脂肪酸氧化。
DOI：
10.1016/j.molcel.2011.01.002
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发表时间：
2011-01-21
期刊：
影响因子：
16
通讯作者：
Denu JM
中科院分区：
文献类型：
--
作者：
Hallows WC;Yu W;Smith BC;Devries MK;Ellinger JJ;Someya S;Shortreed MR;Prolla T;Markley JL;Smith LM;Zhao S;Guan KL;Denu JM
新出现的证据表明，蛋白质乙酰化是一种广泛的调节机制。在此我们利用乙酰肽阵列和代谢组学分析来鉴定线粒体去乙酰化酶Sirt3的底物。我们从尿素循环中鉴定出鸟氨酸转氨甲酰酶（OTC）以及参与β -氧化的酶。对缺乏Sirt3的禁食小鼠（sirt3 - / -）进行的代谢组学分析显示β -氧化和尿素循环发生了改变。生化分析表明，Sirt3直接使OTC去乙酰化并刺激其活性。处于热量限制（CR）下的小鼠Sirt3蛋白水平升高，导致OTC去乙酰化并刺激其活性。相反，sirt3 - / -小鼠在热量限制时无法使OTC去乙酰化。在热量限制下无法刺激OTC会导致乳清酸水平无法降低，这是已知的OTC缺乏的结果。因此，Sirt3在热量限制期间直接调节OTC活性并促进尿素循环，结果表明在低能量摄入时，Sirt3通过促进氨基酸分解代谢和β -氧化来调节线粒体。
Emerging evidence suggests that protein acetylation is a broad-ranging regulatory mechanism. Here we utilize acetyl-peptide arrays and metabolomic analyses to identify substrates of mitochondrial deacetylase Sirt3. We identified ornithine transcarbamoylase (OTC) from the urea cycle, and enzymes involved in β-oxidation. Metabolomic analyses of fasted mice lacking Sirt3 (sirt3−/−) revealed alterations in β-oxidation and the urea cycle. Biochemical analysis demonstrated that Sirt3 directly deacetylates OTC and stimulates its activity. Mice under caloric restriction (CR) increased Sirt3 protein levels, leading to deacetylation and stimulation of OTC activity. In contrast, sirt3−/− mice failed to deacetylate OTC in response to CR. Inability to stimulate OTC under CR led to a failure to reduce orotic acid levels, a known outcome of OTC deficiency. Thus, Sirt3 directly regulates OTC activity and promotes the urea cycle during CR, and the results suggest that under low energy input, Sirt3 modulates mitochondria by promoting amino-acid catabolism and β-oxidation.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
3.9
作者：
Rose, G;Dato, S;De Benedictis, G
通讯作者：
De Benedictis, G
DOI：
10.1016/j.bbrc.2010.01.081
发表时间：
2010-02-26
影响因子：
3.1
作者：
Ogura, Masahito;Nakamura, Yasuhiko;Inagaki, Nobuya
通讯作者：
Inagaki, Nobuya
影响因子：
8
作者：
Jin, Lei;Galonek, Heidi;Westphal, Christoph H.
通讯作者：
Westphal, Christoph H.
影响因子：
3.9
作者：
Hagopian, K;Ramsey, JJ;Weindruch, R
通讯作者：
Weindruch, R