International Institute of Molecular and Cell Biology, 4 Ks. Trojdena Street, 02-109, Warsaw, Poland.
Centre of New Technologies, University of Warsaw, S. Banacha 2c, 02-097, Warsaw, Poland.
Nat Commun. 2018 Jan 22;9(1):324. doi: 10.1038/s41467-017-02694-8.
The generation of reactive oxygen species (ROS) is inevitably linked to life. However, the precise role of ROS in signalling and specific targets is largely unknown. We perform a global proteomic analysis to delineate the yeast redoxome to a depth of more than 4,300 unique cysteine residues in over 2,200 proteins. Mapping of redox-active thiols in proteins exposed to exogenous or endogenous mitochondria-derived oxidative stress reveals ROS-sensitive sites in several components of the translation apparatus. Mitochondria are the major source of cellular ROS. We demonstrate that increased levels of intracellular ROS caused by dysfunctional mitochondria serve as a signal to attenuate global protein synthesis. Hence, we propose a universal mechanism that controls protein synthesis by inducing reversible changes in the translation machinery upon modulating the redox status of proteins involved in translation. This crosstalk between mitochondria and protein synthesis may have an important contribution to pathologies caused by dysfunctional mitochondria.
活性氧（ROS）的产生不可避免地与生命联系在一起。然而，ROS 在信号转导和特定靶标中的精确作用在很大程度上是未知的。我们进行了一项全局蛋白质组学分析，以对酵母氧化还原组进行深入研究，涵盖了超过 2200 种蛋白质中 4300 多个独特的半胱氨酸残基。对暴露于外源性或内源性线粒体来源的氧化应激的蛋白质中的氧化还原活性巯基进行映射，揭示了翻译装置的几个组件中的 ROS 敏感位点。线粒体是细胞内 ROS 的主要来源。我们证明，功能失调的线粒体导致的细胞内 ROS 水平升高可作为信号来减弱全球蛋白质合成。因此，我们提出了一种通用机制，该机制通过在参与翻译的蛋白质的氧化还原状态上进行调节，在翻译机制上诱导可逆变化，从而控制蛋白质合成。线粒体和蛋白质合成之间的这种串扰可能对由功能失调的线粒体引起的病理有重要贡献。
