Antioxidants and oxidative damage in mitochondria

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DESCRIPTION (provided by applicant) The focus of this project resides on the role of small antioxidant molecules on the prevention and/or repair of nitrated proteins in mitochondria. Protein nitration occurs in biological systems exposed to nitric oxide. The addition of a nitro group to a tyrosine residue, yielding 3-nitrotyorosine, has been claimed to be a post-translational modification, part of signal transduction pathways, or a result of "normal" oxidative stress. In this study, the investigators will characterize the mechanism underlying the nitration of proteins in nitric oxide-producing mitochondria, given the important role that these organelles have in the maintenance of cellular ATP, beta-oxidation, heme synthesis, and other functions. The studies will be aimed at understanding the kinetic and structural changes caused by nitration, and how naturally- occurring antioxidants present in fruits and vegetables may prevent/reverse this effect. The antioxidant effect of flavonoids, coumarins, and catechins will be studied in terms hydroxyl substitution, conjugation of rings, and o- methylation of hydroxyl groups to elucidate an association between structure and function.