CoChat
Sign Up
Cited by 1,000Sirtuins and Resveratrol in MedicineCancer-related gene regulationAdvanced Proteomics Techniques and Applications

SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways

Open access
Park, Jeongsoon, Chen, Yue, Tishkoff, Daniel X., Peng, Chao, Tan, Minjia, Dai, Lunzhai, Xie, Zhongyu, Zhang, Yi +4 more·2013·Molecular Cell
DOI 10.1016/j.molcel.2013.06.001PMC PMC3769971
Open this paper in CoChat — free accountOpen PDF

Abstract

SUMMARY Protein function is regulated by diverse posttranslational modifications. The mitochondrial sirtuin SIRT5 removes malonyl and succinyl moieties from target lysines. The spectrum of protein substrates subject to these modifications is unknown. We report systematic profiling of the mammalian succinylome, identifying 2,565 succinylation sites on 779 proteins. Most of these do not overlap with acetylation sites, suggesting differential regulation of succinylation and acetylation. Our analysis reveals potential impacts of lysine succinylation on enzymes involved in mitochondrial metabolism; e.g., amino acid degradation, the tricarboxylic acid cycle (TCA) cycle, and fatty acid metabolism. Lysine succinylation is also present on cytosolic and nuclear proteins; indeed, we show that a substantial fraction of SIRT5 is extra-mitochondrial. SIRT5 represses biochemical activity of, and cellular respiration through, two protein complexes identified in our analysis, pyruvate dehydrogenase complex and succinate dehydrogenase. Our data reveal widespread roles for lysine succinylation in regulating metabolism and potentially other cellular functions.

Integrity signals

Registry

Crossref · 10.1016/j.molcel.2013.06.001

Cites

83 of 83 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 39 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Systematic profiling identified 2,565 succinylation sites on 779 proteins in mouse cells.

    “We report systematic profiling of the mammalian succinylome, identifying 2,565 succinylation sites on 779 proteins.”
    • Also stated in: § Lysine Succinylation Proteome in Mouse Cells · plain
      “After removing overlapping sites, we identified a total of 2,565 Lys succinylation sites from 779 proteins in mouse cells”
    Quote in the paperSubstantial claim
  • Findingown data

    For RAN K23, succinylation stoichiometry rose from 15% to 45% upon Sirt5 knockout.

    “the K23 site on RAN, located within one of the GTP-binding regions, is Lys succinylated, and its stoichiometry increased from 15% to 45% in Sirt5 KO cells.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Ninety-two Ksucc sites lie within five residues of other PTM types.

    “we identified 92 Ksucc sites located within five residues in flanking distance to various types of PTMs”
    Quote in the paperNot a substantial claim
  • Findingown data

    Succinylated proteins also show enrichment for translation, driven by modified ribosomal proteins.

    “Lys-succinylated proteins were enriched for translational processes (adjusted p = 3.4 × 10−30) because of the identification of succinylated ribosome proteins.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Most succinylation sites do not overlap with acetylation sites.

    “Most of these do not overlap with acetylation sites”
    • Also stated in: § Lysine Succinylation Proteome in Mouse Cells · plain
      “We found that only 282 sites overlapped between Ksucc and Kac sites identified in MEFs”
    Quote in the paperSubstantial claim
  • May combine two claims. 26
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Findingown data

    Absolute stoichiometries of 137 Ksucc sites were calculated; 134 increased in SIRT5 deficiency.

    “we were able to calculate absolute stoichiometries of 137 Ksucc sites in both WT and Sirt5 KO MEFs with a dynamic range from 0.02% to 90%, out of which 134 sites showed increased Ksucc stoichiometries in SIRT5 deficiency”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Fasting increased Ksucc levels in both liver and kidney, with a larger effect in liver.

    “We found that Ksucc levels rose in response to fasting in both tissues, and this change was more marked in the liver than the kidney.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At the -1 position, Ksucc sites favor Gly or Ala; at +1 they favor Ala; Arg is scarce at both.

    “The data showed a preference for Gly or Ala at the −1 position and Ala at the +1 position (Figure 4A). Arg is largely depleted at both the −1 and +1 position.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Immunofluorescence showed SIRT5 partly overlapping mitochondria and also present in the cytosol.

    “SIRT5 (green) partially colocalized with MitoTracker Red to produce a yellow signal. However, a detectable fraction of SIRT5 was present cytosolically”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In Sirt5 KO, succinylation covered 37 of 51 Val-Leu-Ile degradation proteins, more than 80% of TCA cycle proteins, and 60% of fatty acid metabolism proteins.

    “in Sirt5 KOs, 37 of 51 proteins in the Val-Leu-Ile degradation pathway, as well as over 80% of all proteins in the tricarboxylic acid (TCA) cycle, and 60% of all proteins in fatty acid metabolism were Lys succinylated”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SIRT5 is present both mitochondrially and extramitochondrially.

    “Thus, SIRT5 is present both mitochondrially and extramitochondrially”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In Sirt5 KO MEFs, over 90% of measurable Ksucc sites rose, with mean KO/WT ratio 3.61 and median 1.93.

    “more than 90% of these showed increasing abundance in Sirt5 KO cells with an average KO/WT SILAC ratio of 3.61 and a median KO/WT SILAC ratio of 1.93.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Significant succinylation enrichment was seen for the frataxin complex, the HMGB1-HMGB2-HSC70-ERP60-GAPDH complex, PDC, and the SDH-mABC1-PIC-ANT-ATPase complex.

    “we identified significant enrichment of Lys succinylation in the frataxin complex (Figure 6B, adjusted p = 1.8 × 10−11), the HMGB1-HMGB2-HSC70-ERP60-GAPDH complex (Figure 6C, adjusted p = 3.8 × 10−10), the PDC (Figure 6D, adjusted p = 3.6 × 10−10), and the SDH-mABC1-PIC-ANT-ATPase complex (Figure 6E, adjusted p = 7.7 × 10−7)”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Core protein complexes are evolutionarily conserved among mammalian species.

  • May combine two claims.

    Findingown data

    Subnetworks found by MCODE include F1F0 ATP synthase, respiratory chain supercomplexes, glutathione S-transferases, ribosomes, and the chaperonin TCP1 complex.

    “we identified a number of highly connected subnetworks among Lys-succinylated proteins, including the F1F0 ATP synthetase, respiratory chain supercomplexes (complexes I, III, and IV), glutathione S transferases, ribosomes, and the chaperonin-containing TCP1 complex”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Succinylation affected 16% of mitochondrial proteins in MEFs, 23% in liver, and 29% overall.

    “Sixteen percent of mitochondrial proteins were Lys succinylated in MEFs, whereas 23% of mitochondrial proteins were Lys succinylated in liver tissue. Altogether, 29% of mitochondrial proteins were Lys succinylated”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In WT cells, 32% of Ksucc sites exceeded 10% stoichiometry; in KO cells, this rose to 56%.

    “32% of the Ksucc sites had stoichiometries greater than 10% in Sirt5 WT cells, whereas this figure increased to 56% in Sirt5 KO cells”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Sirt5 knockout liver analysis found additional SDHA succinylation sites and one SDHB succinylation site.

    “Analysis of Sirt5 KO liver tissue identified several additional sites in SDHA as well as a single Lys succinylation site in SDHB (Tables S1B and S6).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Thirty-five nonredundant histone lysine succinylation sites were found, six of which overlapped with an earlier mouse-cell report.

    “Given the reported mitochondrial localization of SIRT5, it is somewhat surprising that we identified 35 nonredundant histone Lys succinylation sites, six of those sites overlapping with our first report of histone succinylation sites in mouse cells (Xie et al., 2012).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xie et al., 2012 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Fifteen Ksucc sites were found on IDH2, with K180 and K256 within five residues of the catalytic sites Y179 and K251.

    “We identified a total of 15 Ksucc sites on IDH2, 2 Ksucc sites (K180 and K256) being located within five residues in flanking sequence to sites on IDH2 that are critical for catalysis (Y179 and K251, respectively).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Lysine succinylation is widespread in fibroblasts and hepatocytes and occurs on mitochondrial metabolic enzymes and on extramitochondrial proteins including histones and ribosomes.

    “This modification is widespread in fibroblasts and hepatocytes, occurring on both mitochondrial metabolic enzymes as well as extramitochondrial proteins such as histones and ribosomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Sixteen Ksucc sites overlapped with known cofactor-binding or catalytic sites, and 74 Ksucc sites lay within five residues of enzymatic activity sites.

    “Sixteen Ksucc sites overlapped with known cofactor binding or catalytic sites, and 74 Ksucc sites were located within five residues in flanking distance to enzymatic activity sites (Table S7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    3-NPA treatment slightly raised Ksucc levels, whereas malonate treatment or SDHC knockdown did not.

    “3-NPA treatment, but not malonate treatment or SDHC KD, resulted in a slight increase in Ksucc levels.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Some individual sites could turn over much faster.

    “However, the modification of specific sites may occur much more rapidly.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The authors' earlier work established lysine succinylation and malonylation as validated posttranslational modification pathways.

    “Recently, we identified and fully validated Lys succinylation and malonylation as PTM pathways, implying an ancient conserved function (Peng et al., 2011; Zhang et al., 2011).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Peng et al., 2011 source

      Not checked in the free run.

    • cites Zhang et al., 2011 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Lysine succinylation is functional and broadly affects metabolism and possibly other cell processes.

    “Our data reveal widespread roles for lysine succinylation in regulating metabolism and potentially other cellular functions.”
    • Also stated in: § INTRODUCTION · hedged
      “Thus, Lys succinylation is a functional modification with the potential to impact mitochondrial metabolism and diverse extramitochondrial processes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SIRT5 is thought to localize primarily to mitochondria.

    “SIRT5 is thought to localize primarily to mitochondria (Lombard et al., 2007; Michishita et al., 2005; Nakagawa et al., 2009; Schlicker et al., 2008).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Lombard et al., 2007 source

      Not checked in the free run.

    • cites Michishita et al., 2005 source

      Not checked in the free run.

    • cites Nakagawa et al., 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SIRT5 deficiency does not impact bulk mitochondrial protein acetylation.

    “Less is known regarding the functions of SIRT4 and SIRT5, which, unlike SIRT3, do not impact bulk mitochondrial protein acetylation (Lombard et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lombard et al., 2007 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Earlier work from the authors identified Ksucc sites on E. coli IDH.

    “Our previous studies identified Ksucc sites on E. coli IDH (Zhang et al., 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zhang et al., 2011 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    SIRT5 has a major role in controlling lysine succinylation, similar to SIRT3's principal role in mitochondrial lysine acetylation.

    “Our data are consistent with a major role for SIRT5 in regulating Ksucc levels, which is analogous to the principal role of SIRT3 in regulating mitochondrial Lys acetylation (Hebert et al., 2013; Lombard et al., 2007; Smith et al., 2011).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Hebert et al., 2013 source

      Not checked in the free run.

    • cites Lombard et al., 2007 source

      Not checked in the free run.

    • cites Smith et al., 2011 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Dichloroacetate increases PDC activity by decreasing E1α phosphorylation and turnover.

    “which stimulates PDC activity by reducing the phosphorylation and turnover of E1α (Morten et al., 1999; Stacpoole et al., 2008).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Morten et al., 1999 source

      Not checked in the free run.

    • cites Stacpoole et al., 2008 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    The mechanisms by which proteins become lysine-succinylated remain unclear.

    “Thus, mechanisms of Lys succinylation remain unclear.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Mutations in IDH2 cause D-2 hydroxyglutaric aciduria type 2.

    “Mutations in the IDH2 gene, a mammalian IDH homolog, causes D-2 hydroxyglutaric aciduria type 2 (D2HGA2) (Kranendijk et al., 2010)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kranendijk et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    SIRT5 acts outside mitochondria and may affect chromatin functions.

    “These data imply that SIRT5 functions outside mitochondria, potentially impacting chromatin functions.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Germline SDH mutations in SDHA-SDHD and in SDH assembly factor 2 occur in tumor predisposition syndromes.

    “Germline SDH mutations have been identified in the SDH subunits SDHA–SDHD and also in SDH assembly factor 2 in tumor predisposition syndromes (Hao et al., 2009; Korpershoek et al., 2011; Neumann et al., 2004; Niemann and Müller, 2000; Oudijk et al., 2013; Pollard et al., 2005; Ricketts et al., 2008; Ricketts et al., 2010).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Hao et al., 2009 source

      Not checked in the free run.

    • cites Korpershoek et al., 2011 source

      Not checked in the free run.

    • cites Neumann et al., 2004 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dysregulated SDH activity in these mutations increases succinate and mitochondrial reactive oxygen species, activates HIF1α, and induces angiogenesis.

    “Dysregulated SDH activity in the setting of these mutations promotes the accumulation of succinate and mitochondrial reactive oxygen species, activating HIF1α and inducing angiogenesis (Selak et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Selak et al., 2005 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    SIRT5 and E1α phosphorylation reduce PDC activity by separate mechanisms.

    “Thus, SIRT5 and E1α phosphorylation attenuate PDC activity through distinct mechanisms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Lysine succinylation may affect IDH2 activity, with possible consequences for epigenetic regulation and neoplasia.

    “These data suggest a potential impact of Lys succinylation on the activity of IDH2, which may impact epigenetic regulation and neoplasia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    SIRT5 targets PDC and SDH and suppresses their enzymatic activities and the mitochondrial respiration they drive.

    “We conclude that SIRT5 targets PDC and SDH to suppress their biochemical activities and mitochondrial respiration driven by these complexes.”
    • Also stated in: § DISCUSSION · plain
      “SIRT5 suppresses activities of PDC and SDH.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Reduced IDH2 expression causes epigenetic dysfunction through loss of 5-hydroxymethyl-cytosine in melanoma.

    “whereas its downregulation leads to epigenetic dysfunction via the loss of 5-hydroxymethyl-cytosine in melanoma (Lian et al., 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lian et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    IDH1 or IDH2 mutations produce the oncometabolite D-2-hydroxyglutarate.

    “IDH1 or IDH2 mutations lead to production of the oncometabolite D2-hydroxyglutarate (D-2HG) (Yen et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Yen et al., 2010 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Germline mutations in every Sdh subunit gene can cause mitochondrial disease and tumor susceptibility syndromes.

    “Germ-line mutations in all Sdh subunit genes can cause mitochondrial disease and tumor susceptibility syndromes (Gill, 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gill, 2012 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    SIRT5 desuccinylates PDC subunits to inhibit PDC activity, revealing a previously unrecognized aspect of PDC regulation.

    “Our finding that SIRT5 desuccinylates PDC subunits to inhibit PDC activity reveals a previously unappreciated aspect of PDC regulation and raises the eventual possibility of inhibiting SIRT5 activity as an adjunct treatment in T2D.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    About half of daily caloric intake passes through PDC.

    “About 50% of overall daily caloric intake passes through PDC, highlighting the central importance of this holoenzyme in glucose metabolism (Patel and Korotchkina, 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Patel and Korotchkina, 2006

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    PDC dysfunction is associated with type 2 diabetes and other conditions including neoplasia and cardiac ischemia.

    “PDC dysfunction is linked to type 2 diabetes (T2D) and a diverse spectrum of other human pathologies, such as neoplasia and cardiac ischemia (Patel and Korotchkina, 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Patel and Korotchkina, 2006

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PDC activity regulation is the main mechanism controlling glucose oxidation in mammals in vivo.

    “The regulation of PDC activity is the major mechanism regulating glucose oxidation in mammals in vivo (Wieland et al., 1972).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wieland et al., 1972 source

      Not checked in the free run.

40 of 40

  • The authors state this as an assumption.

    Core protein complexes are evolutionarily conserved among mammalian species.

    “on the basis of the assumption of evolutionary conservation of core protein complexes among mammalian species.”

  • The paper relies on this without support.

    Lysine acetylation primarily localizes to the N-terminal tails of histones.

    “This is in contrast to Lys acetylation, which primarily occupies the N-terminal tails of histones”
2 of 2

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?

  • All four enzymes involved in hepatic ketogenesis are heavily modified by lysine acylations including acetylation, succinylation, glutarylation, and malonylation.

    “Interestingly, all the four enzymes involved in this process (Thiolase, HMG-CoA synthase, HMG-CoA lyase, and βOHB dehydrogenase) are heavily modified by lysine acylations including acetylation, succinylation, glutarylation and malonylation ((Rardin, Newman, et al. 2013))((Rardin, He, et al. 2013))((Park et al. 2013))((Tan et al. 2014))((Nishida et al. 2015)).”

    From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Park et al. 2013

  • SIRT5 is present in the nucleus and cytoplasm in addition to mitochondria.

    “Given that SIRT5 is present in the nucleus and cytoplasm in addition to mitochondria ((Matsushita et al. 2011))((Park et al. 2013))((Nishida et al. 2015)), it will be interesting to test whether SIRT5 modulates the activity of the urea cycle via targeting of both mitochondrial and cytosolic enzymes, or whether one compartment’s effects dominate.”

    From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Park et al. 2013

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Park, J., Chen, Y., Tishkoff, D. X., Peng, C., Tan, M., Dai, L., Xie, Z., Zhang, Y., Zwaans, B. M. M., Skinner, M. E., Lombard, D. B., & Zhao, Y.
Affiliations
  • University of Chicago (US)
  • University of Michigan (US)
  • Chinese Academy of Sciences (CN)
Corresponding author
  • Lombard, David B.
  • Zhao, Yingming
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2013-06
Volume
50
Issue
6
Pages
919-930
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2013.06.001
PMC
PMC3769971
OpenAlex
W1984658022
Semantic Scholar
47c40fa699d766e0ebccc68356e6ef46b90364b9
Cited by
1,000
References
81
Citations by year
2026: 60 · 2025: 88 · 2024: 83 · 2023: 85 · 2022: 93 · 2021: 106 · 2020: 66 · 2019: 87 · 2018: 82 · 2017: 60 · 2016: 73 · 2015: 63 · 2014: 37 · 2013: 15
FWCI
29.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1dp3dk094292-01)
  • National Institute on Aging (P30AG013283, T32AG000114, P30AG024824)
  • National Cancer Institute (R21CA177925)
  • National Institute of General Medical Sciences (U54GM103520, R01GM101171)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P60DK020572, DP3-DK-094292, P30DK020572, P30DK089503)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
SIRT5, lysine succinylation, succinylome, post-translational modification, mitochondrial metabolism, TCA cycle, amino acid catabolism, fatty acid metabolism, pyruvate dehydrogenase complex, succinate dehydrogenase, cellular respiration, acetylation
MeSH terms
Acetylation, Amino Acid Sequence, Animals, Cells, Cultured, Glycosylation, Kinetics, Lysine, Mitochondria, Protein Processing, Post-Translational, Pyruvate Dehydrogenase Complex, Succinate Dehydrogenase, Consensus Sequence, Mice, Knockout, Cell Respiration, Proteome, Protein Transport, Sirtuins, Mice, Metabolic Networks and Pathways, Molecular Sequence Annotation, Protein Interaction Maps

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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