Chronic ethanol feeding causes depression of mitochondrial elongation factor Tu in the rat liver: implications for the mitochondrial ribosome.
Chronic ethanol feeding causes depression of mitochondrial elongation factor Tu in the rat liver: implications for the mitochondrial ribosome.
复制标题
慢性乙醇喂养会导致大鼠肝脏中线粒体延伸因子 Tu 的抑制：对线粒体核糖体的影响。
DOI：
10.1152/ajpgi.00108.2010
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Cahill,Alan
中科院分区：
文献类型：
--
作者：
Weiser,Brian;Gonye,Gregory;Sykora,Peter;Crumm,Sara;Cahill,Alan
已知慢性乙醇喂养会对肝脏能量代谢产生负面影响。以前的研究表明，潜在的损害负责这可能是在线粒体的水平。本研究的目的是描述酒精性雄性大鼠及其等热量配对对照的肝脏线粒体结构。我们的实验表明，慢性乙醇喂养导致结构（死亡相关蛋白3）和功能[延伸因子热不稳定（EF-Tu）]线粒体蛋白的显着耗尽。此外，核苷酸延长因子热稳定（EF-Ts）和结构线粒体核糖体蛋白L12（MRPL 12）显着增加。发现MRPL 12的增加与39 S大线粒体亚基水平的增加相关。这些变化伴随着细胞核和线粒体编码的呼吸亚基水平降低、完整呼吸复合物数量减少、肝脏ATP水平降低和线粒体翻译抑制。使用预先推导的动力学数据对乙醇介导的EF-Tu和EF-Ts变化进行数学建模预测，乙醇介导的EF-Tu水平降低可以完全解释线粒体蛋白质合成受损。总之，慢性乙醇喂养导致肝脏内线粒体EF-Tu水平的耗尽，这在数学上被预测为是导致在酒精动物中观察到的线粒体蛋白质合成受损的原因。
Chronic ethanol feeding is known to negatively impact hepatic energy metabolism. Previous studies have indicated that the underlying lesion responsible for this may lie at the level of the mitoribosome. The aim of this study was to characterize the structure of the hepatic mitoribosome in alcoholic male rats and their isocalorically paired controls. Our experiments revealed that chronic ethanol feeding resulted in a significant depletion of both structural (death-associated protein 3) and functional [elongation factor thermo unstable (EF-Tu)] mitoribosomal proteins. In addition, significant increases were found in nucleotide elongation factor thermo stable (EF-Ts) and structural mitochondrial ribosomal protein L12 (MRPL12). The increase in MRPL12 was found to correlate with an increase in the levels of the 39S large mitoribosomal subunit. These changes were accompanied by decreased levels of nuclear- and mitochondrially encoded respiratory subunits, decreased amounts of intact respiratory complexes, decreased hepatic ATP levels, and depressed mitochondrial translation. Mathematical modeling of ethanol-mediated changes in EF-Tu and EF-Ts using prederived kinetic data predicted that the ethanol-mediated decrease in EF-Tu levels could completely account for the impaired mitochondrial protein synthesis. In conclusion, chronic ethanol feeding results in a depletion of mitochondrial EF-Tu levels within the liver that is mathematically predicted to be responsible for the impaired mitochondrial protein synthesis seen in alcoholic animals.
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影响因子：
46.9
作者：
Kitano, H;Funahashi, A;Oda, K
通讯作者：
Oda, K
影响因子：
14.9
作者：
Uchiumi T;Ohgaki K;Yagi M;Aoki Y;Sakai A;Matsumoto S;Kang D
通讯作者：
Kang D
影响因子：
7.4
作者：
Davis, Christiana W.;Hawkins, Brian J.;Ramasamy, Subbiah;Irrinki, Krishna M.;Cameron, Bruce A.;Islam, Khalid;Daswani, Varsha P.;Doonan, Patrick J.;Manevich, Yefim;Madesh, Muniswamy
通讯作者：
Madesh, Muniswamy
慢性乙醇消耗后肝线粒体核糖体结构发生改变。
影响因子：
3.9
作者：
V. Patel;C. Cunningham
通讯作者：
C. Cunningham
影响因子：
29
作者：
Metodiev, Metodi D.;Lesko, Nicole;Larsson, Nils-Goeran
通讯作者：
Larsson, Nils-Goeran