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首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >Alpha-ketoglutarate dehydrogenase complex-dependent succinylation of proteins in neurons and neuronal cell lines
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Alpha-ketoglutarate dehydrogenase complex-dependent succinylation of proteins in neurons and neuronal cell lines

机译：神经元和神经元细胞系中蛋白质的α-酮戊二酸脱氢酶复合物依赖性琥珀酰化

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摘要

Reversible post-translation modifications of proteins are common in all cells and appear to regulate many processes. Nevertheless, the enzyme(s) responsible for the alterations and the significance of the modification are largely unknown. Succinylation of proteins occurs and causes large changes in the structure of proteins; however, the source of the succinyl groups, the targets, and the consequences of these modifications on other proteins remain unknown. These studies focused on succinylation of mitochondrial proteins. The results demonstrate that the -ketoglutarate dehydrogenase complex (KGDHC) can serve as a trans-succinylase that mediates succinylation in an -ketoglutarate-dependent manner. Inhibition of KGDHC reduced succinylation of both cytosolic and mitochondrial proteins in cultured neurons and in a neuronal cell line. Purified KGDHC can succinylate multiple proteins including other enzymes of the tricarboxylic acid cycle leading to modification of their activity. Inhibition of KGDHC also modifies acetylation by modifying the pyruvate dehydrogenase complex. The much greater effectiveness of KGDHC than succinyl-CoA suggests that the catalysis owing to the E2k succinyltransferase is important. Succinylation appears to be a major signaling system and it can be mediated by KGDHC.
机译：蛋白质的可逆翻译后修饰在所有细胞中都很常见，并且似乎在调节许多过程。然而，很大程度上未知引起改变的酶和修饰的意义。蛋白质发生琥珀酰化并导致蛋白质结构发生重大变化;然而，琥珀酰基团的来源，靶标以及这些修饰对其他蛋白质的影响仍然未知。这些研究集中于线粒体蛋白的琥珀酰化。结果表明，-酮戊二酸脱氢酶复合物（KGDHC）可以作为反-琥珀酸酶，以依赖于-酮戊二酸的方式介导琥珀酰化。抑制KGDHC可以减少培养的神经元和神经元细胞系中胞浆和线粒体蛋白的琥珀酰化作用。纯化的KGDHC可以琥珀酰化多种蛋白质，包括三羧酸循环的其他酶，从而改变其活性。抑制KGDHC还可以通过修饰丙酮酸脱氢酶复合物来修饰乙酰化作用。 KGDHC的效率比琥珀酰-CoA大得多，这表明由于E2k琥珀酰转移酶引起的催化作用很重要。琥珀酰化似乎是主要的信号传导系统，它可以由KGDHC介导。

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