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

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30644754", "kind": "science-record", "revision": 5, "content_hash": "sha256:f37f371c7cdd2bad32754a52a5354e970ccf8655b02b6fdeef723b8e17c54c26", "created_at": "2026-11-01T17:32:33Z", "updated_at": "2026-11-01T22:43:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Quantifying Competition among Mitochondrial Protein Acylation Events Induced by Ethanol Metabolism.", "doi": "10.1021/acs.jproteome.8b00800", "pmid": "30644754", "authors": ["Hadi R Ali", "Mohammed A Assiri", "Peter S Harris", "Cole R Michel", "Youngho Yun", "John O Marentette", "Frank K Huynh", "David J Orlicky", "Colin T Shearn", "Laura M Saba", "Richard Reisdorph", "Nichole Reisdorph", "Matthew D Hirschey", "Kristofer S Fritz"], "journal": "Journal of proteome research", "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.", "claims": [{"id": "claim-method", "statement": "Acetyl or succinyl peptides were filtered on volcano plots using a moderated t-test and peptides that had a fold change ≤ or ≥ 2.0 and p-value < 0.05 were considered significant. Bonferroni FWER multiple-testing correction was also applied to generate a list of acetyl site candidates that were differentially expressed with high confidence that could be used to probe the effects of acetylation and succinylation modifications in individual proteins. A one-way ANOVA between diets, genotypes, control diet genotypes, ethanol diet genotypes, as well as a two-way ANOVA were performed to determine the overall effects of genetic differences vs dietary differences at various lysine acetylation and succinylation sites.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30644754", "locator": "sections[8] \"Accurate mass and retention time (AMRT) library generation\" paragraph 5", "quote": "Acetyl or succinyl peptides were filtered on volcano plots using a moderated t-test and peptides that had a fold change ≤ or ≥ 2.0 and p-value < 0.05 were considered significant. Bonferroni FWER multiple-testing correction was also applied to generate a list of acetyl site candidates that were differentially expressed with high confidence that could be used to probe the effects of acetylation and succinylation modifications in individual proteins. A one-way ANOVA between diets, genotypes, control diet genotypes, ethanol diet genotypes, as well as a two-way ANOVA were performed to determine the overall effects of genetic differences vs dietary differences at various lysine acetylation and succinylation sites."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available via ProteomeXchange with identifier PXD012089.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30644754", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Data are available via ProteomeXchange with identifier PXD012089."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Analysis of all peptides and proteins identified in WT and KO samples revealed that 16% of peptides and 40% of proteins identified were acetylated and succinylated (Figure 5).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:30644754", "locator": "sections[20] \"Quantification of Ethanol-Induced Differential Acyl Switching Proteins Reveals Increased Acetylation and Decreased Succinylation at the Same Lysine Residue\" paragraph 2", "quote": "Analysis of all peptides and proteins identified in WT and KO samples revealed that 16% of peptides and 40% of proteins identified were acetylated and succinylated (Figure 5)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Analysis of all peptides and proteins identified in WT and KO samples revealed that 16% of peptides and 40% of proteins identified were acetylated and succinylated (Figure 5).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30644754"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Bonferroni FWER multiple-testing correction was also applied to generate a list of acetyl site candidates that were differentially expressed with high confidence that could be used to probe the effects of acetylation and succinylation modifications in individual proteins. 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SIRT3 KO and SIRT5 KO mice were kindly provided by Dr. Frederick Alt of Bost", "Institute for Research on Aging.38 Knockout mice were backcrossed 10 generations onto the C57BL/6J", "oyed, and 7-week-old wild-type (WT) C57BL/6J mice were purchased from The Jackson Laboratory (Bar H", "ge food intake in WT, SIRT3 KO, and SIRT5 KO mice were all less than 10 %, indicating that food con"], "order_basis": "paper_text_order:1567", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["using mouse tail snips, and was validated by western blotting (Figure 2C, 2F, 2G). SIRT3 was amplified usi", "mpacting differences between the groups. For Western blot densitometry, graphs represent the average o"], "order_basis": "paper_text_order:2158", "id": "assay:2"}, {"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["surements were made by flow injection tandem mass spectrometry using sample preparation methods described p", "r Tissue Supplementary Material SI1Table S2. Mass spectrometry quantification of acetylated peptides, DAVID", "ins with DAVID analysis. (XLSX) SI2Table S3. Mass spectrometry quantification of succinylated peptides with"], "order_basis": "paper_text_order:5483", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Acetyl or succinyl peptides were filtered on volcano plots using a moderated t-test and peptides that had a fold change ≤ or ≥ 2.0 and p-value < 0.05 were considered significant. Bonferroni FWER multiple-testing correction was also applied to generate a list of acetyl site candidates that were differentially expressed with high confidence that could be used to probe the effects of acetylation and succinylation modifications in individual proteins. A one-way ANOVA between diets, genotypes, control diet genotypes, ethanol diet genotypes, as well as a two-way ANOVA were performed to determine the overall effects of genetic differences vs dietary differences at various lysine acetylation and succinylation sites."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}