Nguyen Jade
Laboratory of Chemical and Biological Probes, EPFL, Station 6, CH-1015 Lausanne.
Chimia (Aarau). 2022 Apr 27;76(4):308-311. doi: 10.2533/chimia.2022.308.
Redox homeostasis is essential for cell function and its disruption is associated with multiple pathologies. Redox balance is largely regulated by the relative concentrations of reduced (GSH) and oxidized (GSSG) glutathione. In eukaryotic cells, this ratio is different in each cell compartment. There is a lack of chemical probes able to modulate GSH/GSSG in order to study the impact of redox stress in an organelle specific manner. Here, we highlight the importance of trialkylphosphines to induce reductive stress and how it can be targeted to a specific organelle. Our probe is selectively activated by endogenous nitroreductases, and releases tributylphosphine to trigger redox stress in mitochondria. Mechanistic studies revealed that the induced stress activates a cellular response orchestrated by transcription factor ATF4, which upregulates genes involved in glutathione catabolism.
氧化还原稳态对细胞功能至关重要，其破坏与多种病理状况相关。氧化还原平衡在很大程度上由还原型（GSH）和氧化型（GSSG）谷胱甘肽的相对浓度调节。在真核细胞中，每个细胞区室中的这一比例各不相同。缺乏能够调节GSH/GSSG以细胞器特异性方式研究氧化还原应激影响的化学探针。在此，我们强调三烷基膦诱导还原应激的重要性以及如何将其靶向特定细胞器。我们的探针被内源性硝基还原酶选择性激活，并释放三丁基膦以触发线粒体中的氧化还原应激。机制研究表明，诱导的应激激活了由转录因子ATF4精心编排的细胞反应，该反应上调了参与谷胱甘肽分解代谢的基因。
