The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
A Class of Reactive Acyl-CoA Species Reveals the Non-enzymatic Origins of Protein Acylation
Open accessAbstract
The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergo intramolecular catalysis to form reactive intermediates that non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized a protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the "acylomes" of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation and validated malate dehydrogenase as a key target. These data uncover a fundamental relationship between reactive acyl-CoA species and proteins and define a new regulatory paradigm in metabolism.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Divalent acyl groups such as succinyl- and glutaryl-CoA can use this alternative non-enzymatic reaction mechanism to achieve higher reaction rates than monovalent acyl species such as acetyl-CoA.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Wagner et al. 2017
In the citing paper
“Recent work has further shown that some acyl-CoA species can modify lysines via a cyclic anhydride intermediate (Wagner et al. 2017).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Wagner et al. 2017
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
CHARMM: The biomolecular simulation program
Brooks, B. R., Brooks, C. L., MacKerell, A. D., Nilsson, L., Petrella, R. J., Roux, B., Won, Y., Archontis, G., Bartels, C., Boresch, S., et al. (2009) · Journal of Computational Chemistry · doi:10.1002/jcc.21287 · Cited by 9,115
Lysine acetylation targets protein complexes and co-regulates major cellular functions
Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., & Mann, M. (2009) · Science · doi:10.1126/science.1175371 · Cited by 4,040
PhosphoSitePlus, 2014: mutations, PTMs and recalibrations
Hornbeck, P. V., Zhang, B., Murray, B., Kornhauser, J. M., Latham, V., & Skrzypek, E. (2015) · Nucleic Acids Research · doi:10.1093/nar/gku1267 · Cited by 3,411
Physiological Roles of Mitochondrial Reactive Oxygen Species
Sena, L. A., & Chandel, N. S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.025 · Cited by 2,632
Regulation of cellular metabolism by protein lysine acetylation
Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., et al. (2010) · Science · doi:10.1126/science.1179689 · Cited by 1,910
SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., et al. (2010) · Nature · doi:10.1038/nature08778 · Cited by 1,687
Self-citationSirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase
Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J. H., Choi, B. H., et al. (2011) · Science · doi:10.1126/science.1207861 · Cited by 1,429
MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins
Calvo, S. E., Clauser, K. R., & Mootha, V. K. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1003 · Cited by 1,251
The Preparation of S-Succinyl Coenzyme A
Simon, E. J., & Shemin, D. (1953) · Journal of the American Chemical Society · doi:10.1021/ja01106a522 · Cited by 1,035
Cited by
Sorted by citations
Functions and mechanisms of non-histone protein acetylation
Narita, T., Weinert, B. T., & Choudhary, C. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0081-3 · Cited by 1,232
Mitochondria as a therapeutic target for common pathologies
Murphy, M. P., & Hartley, R. C. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.174 · Cited by 846
Zhong, Q., Xiao, X., Qiu, Y., Xu, Z., Chen, C., Chong, B., Zhao, X., Hai, S., Li, S., An, Z., et al. (2023) · MedComm · doi:10.1002/mco2.261 · Cited by 442
A metabolite-derived protein modification integrates glycolysis with KEAP1–NRF2 signalling
Bollong, M. J., Lee, G., Coukos, J. S., Yun, H., Zambaldo, C., Chang, J. W., Chin, E. N., Ahmad, I., Chatterjee, A. K., Lairson, L. L., et al. (2018) · Nature · doi:10.1038/s41586-018-0622-0 · Cited by 344
Carrico, C., Meyer, J. G., He, W., Gibson, B. W., & Verdin, E. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.016 · Cited by 331
Metadata
- Authors
- Wagner, G. R., Bhatt, D. P., O’Connell, T. M., Thompson, J. W., Dubois, L. G., Backos, D. S., Yang, H., Mitchell, G. A., Ilkayeva, O. R., Stevens, R. D., Grimsrud, P. A., & Hirschey, M. D.
- Affiliations
- Duke University (US)
- Duke Medical Center (US)
- University of Colorado Anschutz (US)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Corresponding author
- Hirschey, Matthew D.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 25
- Issue
- 4
- Pages
- 823-837.e8
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5399522
- OpenAlex
- W2604275396
- Cited by
- 258
- References
- 48
- Citations by year
- 2026: 21 · 2025: 24 · 2024: 28 · 2023: 24 · 2022: 37 · 2021: 35 · 2020: 28 · 2019: 19 · 2018: 27 · 2017: 15
- FWCI
- 8.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (2T32DK007012)
- Ellison Medical Foundation
- American Heart Association (12IRG9010008)
- National Institutes of Health
- Canadian Institutes of Health Research (034368-UNC, 178978)
- National Institute on Alcohol Abuse and Alcoholism (R01AA022146)
- Centre hospitalier régional universitaire de Lille
- National Institute on Aging (P30AG028716-01, R01AG045351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- protein acylation, HMG-CoA, glutaryl-CoA, lysine acylation, intramolecular catalysis, TCA cycle, malate dehydrogenase, HMG-CoA reductase inhibition, metabolic regulation
- MeSH terms
- Acyl Coenzyme A, Acylation, Anhydrides, Citric Acid Cycle, Lysine, Mitochondria, Protein Processing, Post-Translational, Proteins, Proteomics, Biocatalysis, Metabolome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
