Cysteine redoxome landscape in mouse brown adipose tissue under acute cold exposure

• Published in: iScience Vol. 28; no. 3; p. 112051
• Main Authors: Oo, Hein Ko, Galicia-Medina, Cynthia M., Nishiuchi, Takumi, Tanida, Ryota, Goto, Hisanori, Nakano, Yujiro, Takeshita, Yumie, Saito, Yoshiro, Takayama, Hiroaki, Takamura, Toshinari
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.03.2025; Elsevier
• Subjects: Cell biology; Functional aspects of cell biology; Physiology; Proteomics; Cell biology; Physiology; Functional aspects of cell biology; Proteomics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2025.112051

Reversible cysteine post-translational modifications serve as a "switch" for protein structure-function dynamics. While reversible cysteine oxidation in uncoupling protein 1 is known to play a role in brown fat thermogenesis, the full cysteine redoxome affected by cold exposure remains unexplored. We established a strategy for comprehensively mapping the cysteine redoxome by pinpointing oxidized and reduced cysteine residues in the brown adipose tissue of mice under room temperature and acute cold exposure. We identified over 1,000 labeled cysteine residues under room and cold temperatures. Cold exposure shifted the cysteine redox states toward oxidation. Cold-sensitive reactive cysteine residues were enriched in biological processes and molecular functions associated with thermogenesis pathways. The presence of proximal positively charged and negatively charged amino acids determined the highly reactive and non-reactive cysteine residues, respectively, under cold exposure. Our findings broaden the landscape of cold-sensitive proteome and identify potential therapeutic targets to fine-tune thermogenesis. [Display omitted] •Alkylation-based redoxome pinpoints both oxidized and reduced cysteine residues•Cold exposure perturbs cysteine redox status in brown fat•Cold-reactive cysteines are enriched in mitochondrial activation pathways•Nearby positively charged amino acids enhance cysteine redox reactivity Physiology; Cell biology; Functional aspects of cell biology; Proteomics