The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks
Open accessAbstract
Summary Reversible posttranslational modifications are emerging as critical regulators of mitochondrial proteins and metabolism. Here, we use a label-free quantitative proteomic approach to characterize the lysine succinylome in liver mitochondria and its regulation by the desuccinylase SIRT5. A total of 1190 unique sites were identified as succinylated, and 386 sites across 140 proteins representing several metabolic pathways including β-oxidation and ketogenesis were significantly hypersuccinylated in Sirt5−/− animals. Loss of SIRT5 leads to accumulation of medium- and long-chain acylcarnitines and decreased β-hydroxybutyrate production in vivo. In addition, we demonstrate that SIRT5 regulates succinylation of the rate-limiting ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) both in vivo and in vitro. Finally, mutation of hypersuccinylated residues K83 and K310 on HMGCS2 to glutamic acid strongly inhibits enzymatic activity. Taken together, these findings establish SIRT5 as a global regulator of lysine succinylation in mitochondria and present a mechanism for inhibition of ketogenesis through HMGCS2.
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.
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
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302
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
Acetylation and deacetylation of non-histone proteins
Glozak, M. A., Sengupta, N., Zhang, X., & Seto, E. (2005) · Gene · doi:10.1016/j.gene.2005.09.010 · Cited by 1,584
Sirt5 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
Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation
Lombard, D. B., Alt, F. W., Cheng, H.-L., Bunkenborg, J., Streeper, R. S., Mostoslavsky, R., Kim, J., Yancopoulos, G., Valenzuela, D., Murphy, A., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01636-07 · Cited by 1,216
Self-citationIdentification of lysine succinylation as a new post-translational modification
Zhang, Z., Tan, M., Xie, Z., Dai, L., Chen, Y., & Zhao, Y. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.495 · Cited by 1,027
SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways
Park, J., Chen, Y., Tishkoff, D. X., Peng, C., Tan, M., Dai, L., Xie, Z., Zhang, Y., Zwaans, B. M. M., Skinner, M. E., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.001 · Cited by 1,000
SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
Nakagawa, T., Lomb, D. J., Haigis, M. C., & Guarente, L. (2009) · Cell · doi:10.1016/j.cell.2009.02.026 · Cited by 787
The first identification of lysine malonylation substrates and its regulatory enzyme
Peng, C., Lu, Z., Xie, Z., Cheng, Z., Chen, Y., Tan, M., Luo, H., Zhang, Y., He, W., Yang, K., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.012658 · Cited by 751
Self-citationCalorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome
Hebert, A. S., Dittenhafer-Reed, K. E., Yu, W., Bailey, D. J., Selen, E. S., Boersma, M. D., Carson, J. J., Tonelli, M., Balloon, A. J., Higbee, A. J., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.024 · Cited by 636
Cited by
The growing landscape of lysine acetylation links metabolism and cell signalling
Choudhary, C., Weinert, B. T., Nishida, Y., Verdin, E., & Mann, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3841 · Cited by 1,324
Self-citationNAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W., Huang, C., Huber, P. E., Zhou, X., Li, C., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,052
Modulation of cellular processes by histone and non-histone protein acetylation
Shvedunova, M., & Akhtar, A. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00441-y · Cited by 936
β-Hydroxybutyrate: A Signaling Metabolite
Newman, J. C., & Verdin, E. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064916 · Cited by 872
Self-citationNishida, Y., Rardin, M. J., Carrico, C., He, W., Sahu, A. K., Gut, P., Najjar, R., Fitch, M., Hellerstein, M., Gibson, B. W., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.022 · Cited by 481
Self-citation
Metadata
- Authors
- Rardin, M. J., He, W., Nishida, Y., Newman, J. C., Carrico, C., Danielson, S. R., Guo, A., Gut, P., Sahu, A. K., Li, B., Uppala, R., Fitch, M., Riiff, T., Zhu, L., Zhou, J., Mulhern, D., Stevens, R. D., Ilkayeva, O. R., Newgard, C. B., Jacobson, M. P., Hellerstein, M., Goetzman, E. S., Gibson, B. W., & Verdin, E.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 18
- Issue
- 6
- Pages
- 920-933
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2090008797
- Cited by
- 713
- References
- 13
- FWCI
- 17.37
- Type
- journal article
- Language
- en
- Open access
- bronze
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks. https://app.cochat.ai/papers/10.1016/j.cmet.2013.11.013
- The paper
- Rardin, M. J., He, W., Nishida, Y., Newman, J. C., Carrico, C., Danielson, S. R., Guo, A., Gut, P., Sahu, A. K., Li, B., Uppala, R., Fitch, M., Riiff, T., Zhu, L., Zhou, J., Mulhern, D., Stevens, R. D., Ilkayeva, O. R., Newgard, C. B., . . . Verdin, E. (2013). SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks. Cell Metabolism. https://doi.org/10.1016/j.cmet.2013.11.013
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
