Protein disulfide bonds and reactive oxygen species

Protein disulfide bonds and reactive oxygen species (ROS) represent a fundamental biochemical mechanism rather than a single protein target. This interplay involves the formation and isomerization of disulfide bonds between cysteine residues, a process critically influenced by the cellular redox environment and ROS levels (Sies & Jones, 2020). ROS like hydrogen peroxide act as secondary messengers that can oxidize protein thiols, leading to structural changes that regulate protein function, a concept known as 'redox signaling' (Finkel, 2011). Enzymes such as Protein Disulfide Isomerase (PDI) and members of the Thioredoxin superfamily are the actual molecular targets that catalyze these reactions and maintain redox homeostasis (Bulleid & Ellgaard, 2011). In oncology, the upregulation of these pathways allows tumor cells to manage high oxidative stress, making PDI inhibitors a focus for therapeutic intervention to induce proteotoxic stress and apoptosis (Xu et al., 2014). Conversely, in neurodegeneration, the impairment of disulfide bond formation leads to the accumulation of misfolded proteins, suggesting that modulating this redox-disulfide axis could have broad therapeutic implications (Wang et al., 2014).

Other names

Redox-mediated disulfide formationOxidative protein foldingThiol-disulfide exchangeRedox signalingRedox-sensitive disulfide switches

Modulation of cellular redox state or inhibition of enzymes (e.g., Protein Disulfide Isomerase) that catalyze disulfide bond formation/rearrangement.