Proteome adaptations in Ethe1-deficient mice indicate a role in lipid catabolism and cytoskeleton organization via post-translational protein modifications.
Proteome adaptations in Ethe1-deficient mice indicate a role in lipid catabolism and cytoskeleton organization via post-translational protein modifications.
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DOI：
10.1042/bsr20130051
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发表时间：
2013-07-25
影响因子：
4
通讯作者：
Braun HP
中科院分区：
文献类型：
--
作者：
Hildebrandt TM;Di Meo I;Zeviani M;Viscomi C;Braun HP
硫化氢是一种生理相关的信号分子。然而，这种高度生物活性物质的循环水平必须保持在严格控制的限度内，以避免毒副作用。在患有EE（乙基丙二酸脑病）的患者中，在SDO（硫双加氧酶）ETHE 1水平上的硫化物氧化的阻断导致微循环和细胞能量代谢的严重功能障碍。我们使用Ethe 1缺陷小鼠模型来研究硫化物和过硫化物浓度增加对肝脏、肾脏、肌肉和大脑蛋白质组的影响。翻译后蛋白质修饰的主要干扰表明，线粒体硫化物氧化途径可能有一个至关重要的功能，在硫化物信号最有可能通过半胱氨酸S-修饰的调节。我们的研究结果证实硫化物参与氧化还原调节和细胞骨架动力学。此外，他们认为硫化物信号传导特异性地调节FA（脂肪酸）和BCAA（支链氨基酸）的线粒体催化剂。这些发现在EE的背景下特别相关，因为它们可以解释疾病的主要症状。
Hydrogen sulfide is a physiologically relevant signalling molecule. However, circulating levels of this highly biologically active substance have to be maintained within tightly controlled limits in order to avoid toxic side effects. In patients suffering from EE (ethylmalonic encephalopathy), a block in sulfide oxidation at the level of the SDO (sulfur dioxygenase) ETHE1 leads to severe dysfunctions in microcirculation and cellular energy metabolism. We used an Ethe1-deficient mouse model to investigate the effect of increased sulfide and persulfide concentrations on liver, kidney, muscle and brain proteomes. Major disturbances in post-translational protein modifications indicate that the mitochondrial sulfide oxidation pathway could have a crucial function during sulfide signalling most probably via the regulation of cysteine S-modifications. Our results confirm the involvement of sulfide in redox regulation and cytoskeleton dynamics. In addition, they suggest that sulfide signalling specifically regulates mitochondrial catabolism of FAs (fatty acids) and BCAAs (branched-chain amino acids). These findings are particularly relevant in the context of EE since they may explain major symptoms of the disease.