Quantifying Competition among Mitochondrial Protein Acylation Events Induced by Ethanol Metabolism.

Journal Article (Journal Article)

Mitochondrial dysfunction is one of many key factors in the etiology of alcoholic liver disease (ALD). Lysine acetylation is known to regulate numerous mitochondrial metabolic pathways, and recent reports demonstrate that alcohol-induced protein acylation negatively impacts these processes. To identify regulatory mechanisms attributed to alcohol-induced protein post-translational modifications, we employed a model of alcohol consumption within the context of wild type (WT), sirtuin 3 knockout (SIRT3 KO), and sirtuin 5 knockout (SIRT5 KO) mice to manipulate hepatic mitochondrial protein acylation. Mitochondrial fractions were examined by label-free quantitative HPLC-MS/MS to reveal competition between lysine acetylation and succinylation. A class of proteins defined as "differential acyl switching proteins" demonstrate select sensitivity to alcohol-induced protein acylation. A number of these proteins reveal saturated lysine-site occupancy, suggesting a significant level of differential stoichiometry in the setting of ethanol consumption. We hypothesize that ethanol downregulates numerous mitochondrial metabolic pathways through differential acyl switching proteins. Data are available via ProteomeXchange with identifier PXD012089.

Full Text

Duke Authors

Cited Authors

  • Ali, HR; Assiri, MA; Harris, PS; Michel, CR; Yun, Y; Marentette, JO; Huynh, FK; Orlicky, DJ; Shearn, CT; Saba, LM; Reisdorph, R; Reisdorph, N; Hirschey, MD; Fritz, KS

Published Date

  • April 5, 2019

Published In

Volume / Issue

  • 18 / 4

Start / End Page

  • 1513 - 1531

PubMed ID

  • 30644754

Pubmed Central ID

  • PMC6450748

Electronic International Standard Serial Number (EISSN)

  • 1535-3907

Digital Object Identifier (DOI)

  • 10.1021/acs.jproteome.8b00800


  • eng

Conference Location

  • United States