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Quantifying Competition among Mitochondrial Protein Acylation Events Induced by Ethanol Metabolism.
- Source :
-
Journal of proteome research [J Proteome Res] 2019 Apr 05; Vol. 18 (4), pp. 1513-1531. Date of Electronic Publication: 2019 Jan 31. - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Animals
Liver Diseases, Alcoholic metabolism
Male
Metabolic Networks and Pathways drug effects
Mice
Mice, Knockout
Sirtuin 3 genetics
Sirtuin 3 metabolism
Sirtuins genetics
Sirtuins metabolism
Acylation drug effects
Ethanol pharmacology
Mitochondria drug effects
Mitochondria metabolism
Proteome chemistry
Proteome drug effects
Proteome metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3907
- Volume :
- 18
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of proteome research
- Publication Type :
- Academic Journal
- Accession number :
- 30644754
- Full Text :
- https://doi.org/10.1021/acs.jproteome.8b00800