A quantitative tissue-specific landscape of protein redox regulation during aging

ABSTRACT: Mammalian tissues engage in specialized physiology that is regulated by post-translational protein modification. A major mode of protein regulation is initiated by reactive oxygen species (ROS) that reversibly modify protein cysteine residues. ROS regulate a myriad of biological processes and ROS dysregulation has long been implicated in age-related dysfunction. However, the protein targets of ROS modification that underlie tissue-specific physiology in vivo are largely unknown. Here we develop a mass spectrometric technology for the first comprehensive and quantitative mapping of the mouse cysteine redox proteome in vivo. We report the cysteine redox landscape across 10 tissues in young and old mice and establish several unexpected and fundamental paradigms of redox signaling. We define and validate cysteine redox networks within each tissue that are highly tissue-selective and underlie tissue-specific biology. We determine a common mechanism for encoding cysteine redox sensitivity by local electrostatic gating. Finally, we comprehensively identify redox-modified disease networks that remodel in aged mice, providing a systemic molecular basis for the longstanding 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, Heart, Brain, Skeletal Muscle, Brown Adipose Tissue, Lung, Liver, Epididymal White Adipose Tissue, Kidney, Subcutaneous Adipose Tissue

SUBMITTER: Haopeng Xiao  

LAB HEAD: Edward Chouchani

PROVIDER: PXD017050 | Pride | 2020-02-27

REPOSITORIES: Pride