Romero-Aristizabal Catalina, Marks Debora S, Fontana Walter, Apfeld Javier
Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Alpert 513, Boston, Massachusetts 02115, USA.
Nat Commun. 2014 Sep 29;5:5020. doi: 10.1038/ncomms6020.
Cells adjust their behaviour in response to redox events by regulating protein activity through the reversible formation of disulfide bridges between cysteine thiols. However, the spatial and temporal control of these modifications remains poorly understood in multicellular organisms. Here we measured the protein thiol-disulfide balance in live Caenorhabditis elegans using a genetically encoded redox sensor and found that it is specific to tissues and is patterned spatially within a tissue. Insulin signalling regulates the sensor's oxidation at both of these levels. Unexpectedly, we found that isogenic individuals exhibit large differences in the sensor's thiol-disulfide balance. This variation contrasts with the general view that glutathione acts as the main cellular redox buffer. Indeed, our work suggests that glutathione converts small changes in its oxidation level into large changes in its redox potential. We therefore propose that glutathione facilitates the sensitive control of the thiol-disulfide balance of target proteins in response to cellular redox events.
细胞通过调节蛋白质活性，即通过半胱氨酸硫醇之间二硫键的可逆形成来响应氧化还原事件，从而调整其行为。然而，在多细胞生物中，这些修饰的空间和时间控制仍知之甚少。在这里，我们使用基因编码的氧化还原传感器测量了活的秀丽隐杆线虫体内的蛋白质硫醇-二硫键平衡，发现它具有组织特异性，并且在组织内呈空间模式分布。胰岛素信号在这两个层面上调节传感器的氧化。出乎意料的是，我们发现同基因个体在传感器的硫醇-二硫键平衡上表现出很大差异。这种变化与谷胱甘肽作为主要细胞氧化还原缓冲剂的普遍观点形成对比。事实上，我们的研究表明，谷胱甘肽将其氧化水平的微小变化转化为其氧化还原电位的大幅变化。因此，我们提出，谷胱甘肽有助于响应细胞氧化还原事件，对靶蛋白的硫醇-二硫键平衡进行敏感控制。
