Methionine oxidation is a post-translational modification PTM that occurs when methionine residues in proteins are exposed to reactive oxygen species ROS such as hydrogen peroxide. This process results in the conversion of methionine to methionine sulfoxide. Methionine oxidation can have significant effects on protein structure, function, and stability, which in turn can influence protein degradation and turnover in human cells.1. Protein structure and function: Methionine oxidation can lead to changes in protein structure by altering the hydrophobicity of the methionine residue. This can affect protein folding, stability, and interactions with other proteins or ligands. In some cases, these structural changes can lead to a loss of protein function or even gain of new functions. This can trigger cellular quality control mechanisms to target the oxidized proteins for degradation.2. Protein degradation: Oxidized proteins are often recognized as damaged or misfolded proteins by the cellular protein quality control system. This system includes molecular chaperones, the ubiquitin-proteasome system UPS , and autophagy. The UPS is responsible for the selective degradation of proteins that are tagged with ubiquitin molecules. Oxidized proteins are more likely to be ubiquitinated and targeted for degradation by the proteasome. Autophagy, on the other hand, is a process where cellular components, including damaged proteins, are engulfed by autophagosomes and delivered to lysosomes for degradation. Methionine oxidation can enhance the susceptibility of proteins to these degradation pathways, thereby increasing protein turnover.3. Protein turnover: Methionine oxidation can affect protein turnover by influencing both protein synthesis and degradation. Oxidative stress can lead to a general decrease in protein synthesis, as the cellular machinery responsible for translation is also sensitive to ROS. This can result in a reduction in the overall rate of protein synthesis, which can contribute to an increase in protein turnover. Additionally, as mentioned earlier, methionine oxidation can enhance protein degradation, further contributing to increased protein turnover.In summary, methionine oxidation can affect protein degradation and turnover in human cells by altering protein structure and function, increasing the susceptibility of proteins to degradation pathways, and influencing protein synthesis. Understanding the role of methionine oxidation in protein degradation and turnover is important for elucidating the cellular response to oxidative stress and the mechanisms underlying various diseases associated with protein misfolding and aggregation.