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

Juan Feng, Hongwei Xie, Danni L. Meany, LaDora V. Thompson, Edgar A. Arriaga, Timothy J. Griffin

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1137-1152
Number of pages16
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume63
Issue number11
DOIs
StatePublished - Nov 2008

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS This study was supported by grants from the National Cancer Institute (R01-CA90626 to Dr. Du), and the Department of Defense (DAMD17-99-1-9397 to Dr. Du). We thank Jonathan Mahnkan, MS, for help with sensitivity analysis. This study used the Linked SEER-Medicare Database.

Keywords

  • Aging
  • Carbonylation
  • Ingenuity pathway analysis
  • Mass spectrometry
  • Mitochondria
  • Muscle
  • Quantitative proteomics

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