Regulation of translation by one-carbon metabolism in bacteria and eukaryotic organelles.
Regulation of translation by one-carbon metabolism in bacteria and eukaryotic organelles.
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DOI：
10.1074/jbc.rev120.011985
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Varshney U
中科院分区：
文献类型：
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作者：
Shetty S;Varshney U
蛋白质合成是一种耗费能量的细胞活动。因此，mRNA翻译过程与细胞代谢及其能量储备保持良好的同步是很重要的。不受控制的翻译可能导致产生不完整、错误翻译或错误折叠的蛋白质，浪费细胞维持所需的能量并引起细胞毒性。单碳代谢（OCM）是细胞中间体代谢的重要组成部分，可产生多种单碳单位中间体（甲酰基、亚甲基、甲基、甲基）。这些OCM中间体是产生氨基酸（如蛋氨酸）和其他生物分子（如嘌呤、胸苷酸和氧化还原调节剂）所必需的。在这篇综述中，我们讨论了OCM如何影响翻译装置（由核糖体、tRNA、mRNA和翻译因子组成）并调节蛋白质合成的关键步骤。更具体地说，我们讨论了OCM代谢物如何调节细菌和真核细胞器（如线粒体）中翻译起始的保真度和速率。OCM对翻译起始保真度的调节为理解涉及应激耐受性和耐药性的其他翻译机制开辟了新的途径。
Protein synthesis is an energetically costly cellular activity. It is therefore important that the process of mRNA translation remains in excellent synchrony with cellular metabolism and its energy reserves. Unregulated translation could lead to the production of incomplete, mistranslated, or misfolded proteins, squandering the energy needed for cellular sustenance and causing cytotoxicity. One-carbon metabolism (OCM), an integral part of cellular intermediary metabolism, produces a number of one-carbon unit intermediates (formyl, methylene, methenyl, methyl). These OCM intermediates are required for the production of amino acids such as methionine and other biomolecules such as purines, thymidylate, and redox regulators. In this review, we discuss how OCM impacts the translation apparatus (composed of ribosome, tRNA, mRNA, and translation factors) and regulates crucial steps in protein synthesis. More specifically, we address how the OCM metabolites regulate the fidelity and rate of translation initiation in bacteria and eukaryotic organelles such as mitochondria. Modulation of the fidelity of translation initiation by OCM opens new avenues to understand alternative translation mechanisms involved in stress tolerance and drug resistance.