The fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest acetylation coordinates organ-specific fuel switching

Li Yang, Bhavapriya Vaitheesvaran, Kirsten Hartil, Alan J. Robinson, Michael R. Hoopmann, Jimmy K. Eng, Irwin J. Kurland, James E. Bruce

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

The elucidation of extra-nuclear lysine acetylation has been of growing interest, as the cosubstrate for acetylation, acetyl CoA, is at a key metabolic intersection. Our hypothesis was that mitochondrial and cytoplasmic protein acetylation may be part of a fasted/re-fed feedback control system for the regulation of the metabolic network in fuel switching, where acetyl CoA would be provided by fatty acid oxidation, or glycolysis, respectively. To test this, we characterized the mitochondrial and cytoplasmic acetylome in various organs that have a high metabolic rate relative to their mass, and/or switch fuels, under fasted and re-fed conditions (brain, kidney, liver, skeletal muscle, heart muscle, white and brown adipose tissues). Using immunoprecipitation, coupled with LC-MS/MS label free quantification, we show there is a dramatic variation in global quantitative profiles of acetylated proteins from different organs. In total, 733 acetylated peptides from 337 proteins were identified and quantified, out of which 31 acetylated peptides from the metabolic proteins that may play organ-specific roles were analyzed in detail. Results suggest that fasted/re-fed acetylation changes coordinated by organ-specific (de)acetylases in insulin-sensitive versus -insensitive organs may underlie fuel use and switching. Characterization of the tissue-specific acetylome should increase understanding of metabolic conditions wherein normal fuel switching is disrupted, such as in Type II diabetes.

Original languageEnglish (US)
Pages (from-to)4134-4149
Number of pages16
JournalJournal of Proteome Research
Volume10
Issue number9
DOIs
StatePublished - Sep 2 2011

Keywords

  • LC-MS/MS
  • acetyl coA
  • acetylation
  • fasting
  • immunoprecipitation
  • insulin sensitivity
  • label-free quantification proteomics
  • metabolic flexibility
  • mouse organs
  • re-feeding

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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