García-Giménez José Luis, Markovic Jelena, Dasí Francisco, Queval Guillaume, Schnaubelt Daniel, Foyer Christine H, Pallardó Federico V
The Centre for Biomedical Network Research on Rare Diseases, Valencia, Spain.
Biochim Biophys Acta. 2013 May;1830(5):3304-16. doi: 10.1016/j.bbagen.2012.10.005. Epub 2012 Oct 13.
Glutathione (GSH) is a linchpin of cellular defences in plants and animals with physiologically-important roles in the protection of cells from biotic and abiotic stresses. Moreover, glutathione participates in numerous metabolic and cell signalling processes including protein synthesis and amino acid transport, DNA repair and the control of cell division and cell suicide programmes. While it is has long been appreciated that cellular glutathione homeostasis is regulated by factors such as synthesis, degradation, transport, and redox turnover, relatively little attention has been paid to the influence of the intracellular partitioning on glutathione and its implications for the regulation of cell functions and signalling. We focus here on the functions of glutathione in the nucleus, particularly in relation to physiological processes such as the cell cycle and cell death. The sequestration of GSH in the nucleus of proliferating animal and plant cells suggests that common redox mechanisms exist for DNA regulation in G1 and mitosis in all eukaryotes. We propose that glutathione acts as "redox sensor" at the onset of DNA synthesis with roles in maintaining the nuclear architecture by providing the appropriate redox environment for the DNA replication and safeguarding DNA integrity. In addition, nuclear GSH may be involved in epigenetic phenomena and in the control of nuclear protein degradation by nuclear proteasome. Moreover, by increasing the nuclear GSH pool and reducing disulfide bonds on nuclear proteins at the onset of cell proliferation, an appropriate redox environment is generated for the stimulation of chromatin decompaction. This article is part of a Special Issue entitled Cellular functions of glutathione.
谷胱甘肽（GSH）是动植物细胞防御系统的关键物质，在保护细胞免受生物和非生物胁迫方面发挥着重要的生理作用。此外，谷胱甘肽参与众多代谢和细胞信号传导过程，包括蛋白质合成、氨基酸转运、DNA修复以及细胞分裂和细胞自杀程序的控制。虽然长期以来人们一直认识到细胞内谷胱甘肽稳态受合成、降解、转运和氧化还原周转等因素调控，但相对较少关注细胞内分布对谷胱甘肽的影响及其对细胞功能和信号调节的意义。我们在此聚焦于谷胱甘肽在细胞核中的功能，特别是与细胞周期和细胞死亡等生理过程的关系。增殖的动植物细胞细胞核中谷胱甘肽的隔离表明，所有真核生物在G1期和有丝分裂期的DNA调控存在共同的氧化还原机制。我们提出，谷胱甘肽在DNA合成开始时作为“氧化还原传感器”，通过为DNA复制提供合适的氧化还原环境和维护DNA完整性来维持核结构。此外，核内谷胱甘肽可能参与表观遗传现象以及核蛋白酶体对核蛋白降解的控制。而且，在细胞增殖开始时，通过增加核内谷胱甘肽池和减少核蛋白上的二硫键，可产生合适的氧化还原环境以刺激染色质解聚。本文是名为“谷胱甘肽的细胞功能”的特刊的一部分。
