Ethanol metabolism modifies hepatic protein acylation in mice.
Ethanol metabolism modifies hepatic protein acylation in mice.
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DOI：
10.1371/journal.pone.0075868
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hirschey MD
中科院分区：
文献类型：
--
作者：
Fritz KS;Green MF;Petersen DR;Hirschey MD
线粒体蛋白乙酰化在小鼠慢性乙醇摄入中增加，并被认为降低线粒体功能并有助于酒精性肝病的发病机制。线粒体脱乙酰酶SIRT3调节几种线粒体蛋白的乙酰化状态，包括参与乙醇代谢的那些。新发现的线粒体sirtuin SIRT 5的脱琥珀酰酶活性表明，蛋白琥珀酰化可能是一个重要的翻译后修饰调节线粒体代谢。为了评估蛋白琥珀酰化在乙醇代谢中的可能作用，我们调查了小鼠肝脏亚细胞蛋白组分，这些小鼠喂食对照或补充乙醇的饮食，以获得琥珀酰赖氨酸以及乙酰基、丙酰和丁酰赖氨酸的翻译后修饰。我们发现线粒体蛋白丙酰化增加，类似于线粒体蛋白乙酰化。相反，线粒体蛋白琥珀酰化减少。这些线粒体蛋白质修饰似乎主要由乙醇代谢驱动，而不是由线粒体sirtuin水平的变化驱动。在细胞核中观察到类似的酰基修饰趋势。然而，在细胞质或微粒体隔室中观察到相对较少的酰基修饰，并且通常不受乙醇代谢的影响。使用质谱蛋白质组学方法，我们确定了几个候选乙酰化，丙酰化和琥珀酰化的蛋白质，这些蛋白质使用针对每种修饰的抗体进行富集。此外，我们确定了几个乙酰基和丙酰赖氨酸残基在相同的网站上的一些蛋白质和支持的想法重叠的赖氨酸特异性酰化的性质。因此，我们发现，新的翻译后修饰存在于肝线粒体，细胞核，细胞质和微粒体室和乙醇摄入，及其相关的代谢，诱导这些酰基修饰的特定变化。这些数据表明，除了蛋白质乙酰化，蛋白质酰化有助于整体代谢调控网络，并可能在酒精性肝病的发病机制中发挥重要作用。
Mitochondrial protein acetylation increases in response to chronic ethanol ingestion in mice, and is thought to reduce mitochondrial function and contribute to the pathogenesis of alcoholic liver disease. The mitochondrial deacetylase SIRT3 regulates the acetylation status of several mitochondrial proteins, including those involved in ethanol metabolism. The newly discovered desuccinylase activity of the mitochondrial sirtuin SIRT5 suggests that protein succinylation could be an important post-translational modification regulating mitochondrial metabolism. To assess the possible role of protein succinylation in ethanol metabolism, we surveyed hepatic sub-cellular protein fractions from mice fed a control or ethanol-supplemented diet for succinyl-lysine, as well as acetyl-, propionyl-, and butyryl-lysine post-translational modifications. We found mitochondrial protein propionylation increases, similar to mitochondrial protein acetylation. In contrast, mitochondrial protein succinylation is reduced. These mitochondrial protein modifications appear to be primarily driven by ethanol metabolism, and not by changes in mitochondrial sirtuin levels. Similar trends in acyl modifications were observed in the nucleus. However, comparatively fewer acyl modifications were observed in the cytoplasmic or the microsomal compartments, and were generally unchanged by ethanol metabolism. Using a mass spectrometry proteomics approach, we identified several candidate acetylated, propionylated, and succinylated proteins, which were enriched using antibodies against each modification. Additionally, we identified several acetyl and propionyl lysine residues on the same sites for a number of proteins and supports the idea of the overlapping nature of lysine-specific acylation. Thus, we show that novel post-translational modifications are present in hepatic mitochondrial, nuclear, cytoplasmic, and microsomal compartments and ethanol ingestion, and its associated metabolism, induce specific changes in these acyl modifications. These data suggest that protein acylation, beyond protein acetylation, contributes to the overall metabolic regulatory network and could play an important role in the pathogenesis of alcoholic liver disease.
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影响因子：
16
作者：
Hirschey MD;Shimazu T;Jing E;Grueter CA;Collins AM;Aouizerat B;Stančáková A;Goetzman E;Lam MM;Schwer B;Stevens RD;Muehlbauer MJ;Kakar S;Bass NM;Kuusisto J;Laakso M;Alt FW;Newgard CB;Farese RV Jr;Kahn CR;Verdin E
通讯作者：
Verdin E
影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
SIRT3在饮食限制期间促进尿素周期和脂肪酸氧化。
影响因子：
16
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
通讯作者：
Denu JM
DOI：
10.1016/j.bbrc.2008.06.006
发表时间：
2008-08-22
影响因子：
3.1
作者：
Lieber, Charles S.;Leo, Maria Anna;DeCarli, Leonore M.
通讯作者：
DeCarli, Leonore M.
DOI：
10.1042/bj20120118
发表时间：
2012-05-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Scott I;Webster BR;Li JH;Sack MN
通讯作者：
Sack MN