Mitochondrial peptide methionine sulfoxide reductase

Mitochondrial peptide methionine sulfoxide reductase (MSRA) is a repair enzyme that catalyzes the reversible oxidation-reduction of methionine sulfoxide residues in proteins, restoring function to proteins inactivated by oxidative damage (UniProt: Q9UJ68). The protein plays a crucial role in maintaining protein integrity, particularly in lens proteins such as alpha-crystallin and cytochrome c.

MSRA is localized to mitochondria and functions as an antioxidant defense mechanism within cells. Its expression and activity are relevant to conditions involving oxidative stress and protein aggregation, particularly in age-related pathology where accumulated oxidative damage is a hallmark feature.

In Alzheimer's disease, MSRA is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.30 across subcellular fractions (Chaparral AD proteomics). This upregulation likely reflects increased oxidative stress and a compensatory response to accumulating protein damage characteristic of AD pathology, suggesting the protein's potential involvement in AD-related neurodegeneration mechanisms.