Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion.
Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion.
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DOI：
10.1093/nar/gkw745
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发表时间：
2017-01-09
影响因子：
14.9
通讯作者：
Tomizawa K
中科院分区：
文献类型：
--
作者：
Takahashi N;Wei FY;Watanabe S;Hirayama M;Ohuchi Y;Fujimura A;Kaitsuka T;Ishii I;Sawa T;Nakayama H;Akaike T;Tomizawa K
在tRNA的A37处的2-甲硫基（ms2）修饰对于准确解码是至关重要的，并且有助于哺乳动物的代谢稳态。然而，ms2修饰的调控机制在很大程度上仍然未知。在这里，我们报告，半胱氨酸氢过硫化物（CysSSH），一个新发现的活性硫物种，参与细胞中的ms2修饰。细胞内CysSSH生产的抑制迅速减少ms2的修改，这是抢救的应用程序的外源CysSSH供体。使用一个独特的和稳定的同位素标记的CysSSH供体，我们表明，CysSSH是能够特异性地转移其活性硫原子的半胱氨酸残基的ms2修饰酶以及ms2修饰。此外，在胰腺β细胞系和小鼠模型中，CysSSH产生的抑制损害胰岛素分泌并引起葡萄糖耐受不良。这些结果表明，细胞内CysSSH是一种新的硫源ms2的修饰，它有助于胰岛素分泌。
The 2-methylthio (ms2) modification at A37 of tRNAs is critical for accurate decoding, and contributes to metabolic homeostasis in mammals. However, the regulatory mechanism of ms2 modification remains largely unknown. Here, we report that cysteine hydropersulfide (CysSSH), a newly identified reactive sulfur species, is involved in ms2 modification in cells. The suppression of intracellular CysSSH production rapidly reduced ms2 modification, which was rescued by the application of an exogenous CysSSH donor. Using a unique and stable isotope-labeled CysSSH donor, we show that CysSSH was capable of specifically transferring its reactive sulfur atom to the cysteine residues of ms2-modifying enzymes as well as ms2 modification. Furthermore, the suppression of CysSSH production impaired insulin secretion and caused glucose intolerance in both a pancreatic β-cell line and mouse model. These results demonstrate that intracellular CysSSH is a novel sulfur source for ms2 modification, and that it contributes to insulin secretion.