title: The fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest acetylation coordinates organ-specific fuel switching.
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.
authors: Department of Chemistry, Washington State University, Pullman, Washington 99164, USA.
authors: Li
authors: L
authors: Yang
authors: Bhavapriya
authors: B
authors: Vaitheesvaran
authors: Kirsten
authors: K
authors: Hartil
authors: Alan J
authors: AJ
authors: Robinson
authors: Michael R
authors: MR
authors: Hoopmann
authors: Jimmy K
authors: JK
authors: Eng
authors: Irwin J
authors: IJ
authors: Kurland
authors: James E
authors: JE
authors: Bruce
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002853:Chromatography, Liquid; D003593:Cytoplasm / Q000378:metabolism; D004734:Energy Metabolism; D005215:Fasting / Q000378:metabolism; D047468:Immunoprecipitation; D008239:Lysine / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008815:Mice, Inbred Strains; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D011506:Proteins; D020543:Proteome; D000105:Acetyl Coenzyme A; D008239:Lysine