Biozentrum, University of Basel, Basel, Switzerland.
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India; Jawaharlal Nehru Centre for Advanced Scientific Studies, Jakkur, Bangalore, India.
J Biol Chem. 2021 Jan-Jun;296:100088. doi: 10.1074/jbc.REV120.011985. Epub 2020 Nov 21.
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.
蛋白质合成是一种耗能的细胞活动。因此，mRNA 翻译过程与细胞代谢及其能量储备保持极好的同步性非常重要。不受调节的翻译可能导致产生不完整、翻译错误或错误折叠的蛋白质，浪费细胞维持所需的能量并导致细胞毒性。一碳代谢（OCM）是细胞中间代谢的一个组成部分，产生许多一碳单位中间产物（甲酰基、亚甲基、次甲基、甲基）。这些 OCM 中间产物是产生蛋氨酸等氨基酸和嘌呤、胸苷酸和氧化还原调节剂等其他生物分子所必需的。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）以及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应激耐受和耐药性中涉及的替代翻译机制开辟了新途径。
