Mammalian tissues engage in specialized physiology that is regulated through reversible modification of protein cysteine residues by reactive oxygen species (ROS). ROS regulate a myriad of biological processes, but the protein targets of ROS modification that drive tissue-specific physiology in vivo are largely unknown. Here, we develop Oximouse, a comprehensive and quantitative mapping of the mouse cysteine redox proteome in vivo. We use Oximouse to establish several paradigms of physiological redox signaling. We define and validate cysteine redox networks within each tissue that are tissue selective and underlie tissue-specific biology. We describe a common mechanism for encoding cysteine redox sensitivity by electrostatic gating. Moreover, we comprehensively identify redox-modified disease networks that remodel in aged mice, establishing a systemic molecular basis for the long-standing proposed links between redox dysregulation and tissue aging. We provide the Oximouse compendium as a framework for understanding mechanisms of redox regulation in physiology and aging.

中文翻译：

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老化过程中蛋白质氧化还原调节的组织特定定量景观。

哺乳动物组织参与专门的生理，该生理通过活性氧（ROS）对蛋白质半胱氨酸残基的可逆修饰来调节。ROS调节着无数的生物过程，但是在体内驱动组织特异性生理的ROS修饰的蛋白质靶标却鲜为人知。在这里，我们开发了Oximouse，这是小鼠体内半胱氨酸氧化还原蛋白质组的全面定量映射。我们使用Oximouse建立生理氧化还原信号的几个范例。我们定义和验证每个组织内的半胱氨酸氧化还原网络，这些网络具有组织选择性，是组织特异性生物学的基础。我们描述了一种通过静电门控来编码半胱氨酸氧化还原敏感性的通用机制。此外，我们全面确定了在衰老小鼠中重塑的氧化还原修饰的疾病网络，为氧化还原异常和组织衰老之间长期存在的联系建立系统的分子基础。我们提供Oximouse纲要作为框架，以了解生理和衰老中氧化还原调节的机制。