衰老过程中蛋白质氧化还原调节的定量组织特异

作者：张馨予

本期文章：《细胞》：Online/在线发表

美国哈佛医学院Edward T. Chouchani团队绘制了衰老过程中蛋白质氧化还原调节的定量组织特异性图谱。相关论文于2020年2月27日发表在《细胞》杂志上。

研究团队开发了Oximouse，这是小鼠体内半胱氨酸氧化还原蛋白质组的全面定量图谱。他们使用Oximouse建立生理氧化还原信号的几个范例。他们定义并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。他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普遍机制。

此外，他们全面鉴定了在衰老小鼠中重塑的氧化还原修饰的疾病网络，为氧化还原失调与组织衰老之间长期存在的联系建立了系统的分子基础。他们提供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。

据悉，哺乳动物组织参与专门的生理过程，该生理过程通过活性氧（ROS）对蛋白质半胱氨酸残基的可逆修饰来调节。ROS调节着无数的生物学过程，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。

附：英文原文

Title: A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging

Author: Haopeng Xiao, Mark P. Jedrychowski, Devin K. Schweppe, Edward L. Huttlin, Qing Yu, David E. Heppner, Jiaming Li, Jiani Long, Evanna L. Mills, John Szpyt, Zhixiang He, Guangyan Du, Ryan Garrity, Anita Reddy, Laura Pontano Vaites, Joao A. Paulo, Tinghu Zhang, Nathanael S. Gray, Steven P. Gygi, Edward T. Chouchani

Issue&Volume: 2020-02-27

Abstract: Mammalian tissues engage in specialized physiology that is regulated through reversiblemodification of protein cysteine residues by reactive oxygen species (ROS). ROS regulatea myriad of biological processes, but the protein targets of ROS modification thatdrive tissue-specific physiology in vivo are largely unknown. Here, we develop Oximouse, a comprehensive and quantitativemapping 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 tissueselective and underlie tissue-specific biology. We describe a common mechanism forencoding cysteine redox sensitivity by electrostatic gating. Moreover, we comprehensivelyidentify redox-modified disease networks that remodel in aged mice, establishing asystemic molecular basis for the long-standing proposed links between redox dysregulationand tissue aging. We provide the Oximouse compendium as a framework for understandingmechanisms of redox regulation in physiology and aging.

DOI: 10.1016/j.cell.2020.02.012

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30156-2

期刊信息

Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：36.216

官方网址：https://www.cell.com/

投稿链接：https://www.editorialmanager.com/cell/default.aspx