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

TitleThe fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest acetylation coordinates organ-specific fuel switching.
Publication TypeJournal Article
Year of Publication2011
AuthorsYang, L, Vaitheesvaran, B, Hartil, K, Robinson, AJ, Hoopmann, MR, Eng, JK, Kurland, IJ, Bruce, JE
JournalJ Proteome Res
Volume10
Issue9
Pagination4134-49
Date Published2011 Sep 2
ISSN1535-3907
KeywordsAcetyl Coenzyme A, Acetylation, Amino Acid Sequence, Animals, Chromatography, Liquid, Cytoplasm, Energy Metabolism, Fasting, Immunoprecipitation, Lysine, Male, Metabolic Networks and Pathways, Mice, Mice, Inbred Strains, Mitochondrial Proteins, Molecular Chaperones, Molecular Sequence Data, Organ Specificity, Peptide Fragments, Proteins, Proteome, Proteomics, Tandem Mass Spectrometry
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.

DOI10.1021/pr200313x
Alternate JournalJ. Proteome Res.
Citation Key10.1021/pr200313x
PubMed ID21728379
PubMed Central IDPMC3204869
Grant ListDK58132-01A2 / DK / NIDDK NIH HHS / United States
MC_U105674181 / / Medical Research Council / United Kingdom
P60 DK020541 / DK / NIDDK NIH HHS / United States
P60DK020541 / DK / NIDDK NIH HHS / United States
R01 GM086688 / GM / NIGMS NIH HHS / United States
R01 GM086688-02 / GM / NIGMS NIH HHS / United States
R01 GM086688-03 / GM / NIGMS NIH HHS / United States
R01 RR023334 / RR / NCRR NIH HHS / United States
R01 RR023334-04 / RR / NCRR NIH HHS / United States
R01GM086688 / GM / NIGMS NIH HHS / United States
R01RR023334 / RR / NCRR NIH HHS / United States
S10 RR025107 / RR / NCRR NIH HHS / United States
S10 RR025107-02 / RR / NCRR NIH HHS / United States
S10RR025107 / RR / NCRR NIH HHS / United States
U19AI091175-01 / AI / NIAID NIH HHS / United States
/ / Medical Research Council / United Kingdom