Quantitative proteomic profiling of muscle type-dependent and age-dependent protein carbonylation in rat skeletal muscle mitochondria

Carbonylation is a highly prevalent protein modification in skeletal muscle mitochondria, possibly contributing to its functional decline with age. Using quantitative proteomics, we identified mitochondrial proteins susceptible to carbonylation in a muscle type (slow- vs fast-twitch)-dependent and age-dependent manner from Fischer 344 rat skeletal muscle. Fast-twitch muscle contained twice as many carbonylated mitochondrial proteins than did slow-twitch muscle, with 22 proteins showing significant changes in carbonylation state with age, the majority of these increasing in their amount of carbonylation. Ingenuity pathway analysis revealed that these proteins belong to functional classes and pathways known to be impaired in muscle aging, including cellular function and maintenance, fatty acid metabolism, and citrate cycle. Although our studies do not conclusively link protein carbonylation to these functional changes in aging muscle, they provide a unique catalogue of promising protein targets deserving further investigation because of their potential role in aging muscle decline.