A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging
| Autor: | Haopeng Xiao, David E. Heppner, Mark P. Jedrychowski, Nathanael S. Gray, Steven P. Gygi, Anita Reddy, Jiani Long, Edward L. Huttlin, Guangyan Du, Jiaming Li, John Szpyt, Laura Pontano Vaites, Edward T. Chouchani, Qing Yu, Tinghu Zhang, Ryan Garrity, Joao A. Paulo, Zhixiang He, Evanna L. Mills, Devin K. Schweppe |
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| Rok vydání: | 2019 |
| Předmět: |
Proteomics
Aging Proteome Gating Biology Redox General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine Tissue specific Animals Humans Cysteine 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Mechanism (biology) Proteins Cell biology Oxidative Stress chemistry Organ Specificity Reactive Oxygen Species Oxidation-Reduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Cell. 180(5) |
| ISSN: | 1097-4172 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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