The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index; 4 of the 39 sources its claims cite were checked for support.
SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways
Open accessAbstract
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.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
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- Also stated in: § Lysine Succinylation Proteome in Mouse Cells · plain
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In the paper
“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.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
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In the paper
“we identified 92 Ksucc sites located within five residues in flanking distance to various types of PTMs”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Flanking Sequence and PTM Correlation Analysis
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In the paper
“Lys-succinylated proteins were enriched for translational processes (adjusted p = 3.4 × 10−30) because of the identification of succinylated ribosome proteins.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Functional Annotation of the Lys Succinylome
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In the paper
“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”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
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- Also stated in: § Lysine Succinylation Proteome in Mouse Cells · plain
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In the paper
“We performed fuzzy c-means clustering analysis of the labeling ratios from all 15 peptides and identified four core clusters (Figure S6A).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Kinetics of Lys Succinylation
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In the paper
“we identified 18 Ksucc sites overlapped with other modifications (Table S2)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Flanking Sequence and PTM Correlation Analysis
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“over 12% of the sites showed over 4-fold increase in abundance in SIRT5-deficient cells”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
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In the paper
“we were able to identify 15 Ksucc peptides in both light and heavy form from all three time points (Table S4).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Kinetics of Lys Succinylation
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In the paper
“Succinylation at K265, located near a CoA-binding site (K260) increased in abundance by more than 120-fold in Sirt5 KO cells (about 104-fold after normalization with protein abundance changes).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
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In the paper
“we show that a substantial fraction of SIRT5 is extra-mitochondrial.”
- Also stated in: § SIRT5 Is Present Extramitochondrially · plain
“Subcellular fractionation revealed that a significant fraction of endogenous SIRT5 was present cytosolically both in human cells (Figure 5A) and mouse liver (Figure 5B).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
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- Also stated in: § SIRT5 Is Present Extramitochondrially · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SIRT5 represses biochemical activity of, and cellular respiration through, two protein complexes identified in our analysis, pyruvate dehydrogenase complex and succinate dehydrogenase.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Quantitative analysis showed an increase in Lys succinylation among most protein networks in SIRT5 deficiency”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Protein Interaction Networks of Lys Succinylation Proteome
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In the paper
“a significant portion of cytosolic Ksucc proteins localized exclusively or partially to mitochondria (p = 2.3 × 10−112, Fisher’s exact test)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Cellular Localization of the Lys Succinylation Proteome
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In the paper
“Our data set showed a vast, highly connected network with clusters of nodes extending out to form protein complex patterns”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Protein Interaction Networks of Lys Succinylation Proteome
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In the paper
“the average rate of Lys D4 succinylation incorporation (or the average rate of the Lys H4 succinylation loss) is about 0.92% per hr for the Ksucc sites in Cluster 2”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Kinetics of Lys Succinylation
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In the paper
“Lysine succinylation is also present on cytosolic and nuclear proteins”
- Also stated in: § Cellular Localization of the Lys Succinylation Proteome · plain
“we identified similar numbers of proteins that were not annotated as mitochondrial (Figure 4B), including ribosomes and histone proteins H2A, H2B, H3, and H1”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
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- Also stated in: § Cellular Localization of the Lys Succinylation Proteome · plain
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In the paper
“These data showed that SIRT5 deficiency significantly impacted Ksucc levels”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
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In the paper
“Our analysis showed over 20 enriched protein complexes from Lys-succinylated proteins (adjusted p < 0.01).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Protein Complex Analysis
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- The authors state this as an assumption: Core protein complexes are evolutionarily conserved among mammalian species.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SIRT5 represses biochemical activity of, and cellular respiration through, two protein complexes identified in our analysis, pyruvate dehydrogenase complex and succinate dehydrogenase.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the stoichiometry of K498 site increased from 12% to 31% in Sirt5 KO MEFs”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
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In the paper
“about 85% of the proteins (3,348 out of 3,944) showed less than 1-fold change in abundance in Sirt5 KO MEFs (SILAC Sirt5 KO/WT ratio between 0.5 and 2)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
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In the paper
“we were not able to identify any nuclear protein complexes that were enriched among Ksucc proteins.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Protein Complex Analysis
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- The authors state this as an assumption: Core protein complexes are evolutionarily conserved among mammalian species.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the molecular functions carried out by Lys succinylated proteins included cofactor binding (adjusted p = 1.2 × 10−65) and oxidoreductase activity (adjusted p = 4.2 × 10−71)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Functional Annotation of the Lys Succinylome
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In the paper
“our data showed that SIRT5 deficiency does not significantly impact global Lys acetylation and has an average KO/WT SILAC ratio of 1.04”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
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In the paper
“only 38 Lys-succinylated proteins identified in this study were previously annotated as exclusively nuclear.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Cellular Localization of the Lys Succinylation Proteome
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In the paper
“motif analysis identified AK, GK, KF, and KA motifs as significantly overrepresented for Lys succinylation sites (Bonferroni corrected p < 0.05)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Flanking Sequence and PTM Correlation Analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“normalization by protein quantification ratios did not significantly alter the quantification ratio distribution of Lys succinylation sites”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
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In the paper
“nearly all annotated pathways involving succinyl-CoA in mice were enriched with Lys-succinylated proteins”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Functional Annotation of the Lys Succinylome
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Lys-succinylated proteins were enriched for acyl-CoA dehydrogenase (adjusted p = 5.3 × 10−17), isomerase (adjusted p = 9.2 × 10−12), and aldehyde dehydrogenase (adjusted p = 2.9 × 10−9)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Functional Annotation of the Lys Succinylome
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SIRT5 represses biochemical activity of, and cellular respiration through, two protein complexes identified in our analysis, pyruvate dehydrogenase complex and succinate dehydrogenase.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Among all Ksucc sites colocalized with phosphorylation sites, a surprisingly high percentage (18%) colocalized near known or predicted phosphotyrosine residues.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Flanking Sequence and PTM Correlation Analysis
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In the paper
“Our data indicate that the HADH amino acid residue K81, which is adjacent to a CoA binding site at K80, is succinylated, and its modification increased by more than 200-fold in Sirt5 KO fibroblasts (about 74-fold after normalization with protein abundance changes).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
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In the paper
“Lys-succinylated proteins are significantly enriched in cellular metabolic process with specific enrichment in oxoacid metabolism (adjusted p = 1.6 × 10−110), oxidation reduction process (adjusted p = 8.2 × 10−86), and coenzyme metabolism (adjusted p = 5.4 × 10−57)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Functional Annotation of the Lys Succinylome
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In the paper
“A very small amount of SIRT5 was also detected in the nuclear fraction, which was particularly evident in the liver samples (Figure 5B).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Is Present Extramitochondrially
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In the paper
“Similar trends were apparent for acetylation.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Lysine Succinylation Proteome in Mouse Cells
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In SIRT5-deficient MEFs, 28 Ksucc sites showed a more than 10-fold increase in abundance”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This was associated with a large (roughly 3.5-fold) elevation in cellular respiration in the presence of the SDH substrate succinate (cells were permeabilized to allow compounds access to mitochondria) (Figures 7H and 7I).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
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In the paper
“Consistent with a role for SIRT5 in regulating Ksucc levels extra-mitochondrially, we find that a substantial fraction of SIRT5 protein is cytosolic.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
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In the paper
“Similar to previous findings, Lys succinylation sites on histones primarily localize to the C-terminal globular domains, the exception being the histone H2B K5.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
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In the paper
“In contrast, no significant differences in respiration between WT and Sirt5 KO were observed with ascorbate.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
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In the paper
“SIRT5-deficient mitochondria showed significantly increased respiration in the presence of succinate and pyruvate.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment of purified PDC with SIRT5 decreased holoenzyme activity in vitro (Figure 7C).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sirt5 KD did not impact respiration in the presence of the complex IV substrate ascorbate.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sirt5 KD led to a substantial increase in SDH activity (Figure 7G).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We immunoblotted commercially available PDC and confirmed that we could detect succinylation on multiple PDC subunits (Figure 7B).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increased respiration was also observed in Sirt5 KD cells in the presence of the PDC substrate pyruvate (Figures 7H and 7I).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additional succinylation sites on PDC were identified in MS/MS analysis of Sirt5 KO livers (Tables S1B and S5).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using SILAC analysis, we identified multiple subunits of PDC as hypersuccinylated in Sirt5 KO MEFs (Figure 7A, Tables S1A and S5).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sirt5 KD resulted in elevated PDC activity (Figure 7E).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistent with our SILAC data, WT SIRT5 robustly desuccinylated PDC in vitro (Figure 7B);”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our analysis of Lys succinylation and acetylation in Sirt5 WT and KO cells suggests that there is a limited overlap between the two modifications, implying different regulatory mechanisms.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SILAC studies identified four Lys succinylation sites on the SDHA subunit of SDH (Figure 7F).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This increase was synergistic with treatment with dichloroacetate (DCA)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lys succinylation on histones increases significantly in SIRT5 deficiency with an average SILAC KO/WT ratio of 5.09.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The mitochondrial sirtuin SIRT5 removes malonyl and succinyl moieties from target lysines.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and purine metabolism via urate oxidase (Nakamura et al., 2012).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > INTRODUCTION
What the sources say
- Not checked yetcites Nakamura et al., 2012 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, Lys succinylation might contribute to the fasting response.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Lysine Succinylation Proteome in Mouse Cells
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“However, these studies were not sufficient to fully establish the chemical structure of the modification.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > INTRODUCTION
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Our work, as well as that of others, has identified SIRT5 as the only known enzyme to date catalyzing Lys desuccinylation and demalonylation (Du et al., 2011; Peng et al., 2011; Zhang et al., 2011).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > INTRODUCTION
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, Lys succinylation may regulate functions of its targets on a relatively slow time frame (hr to days).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Kinetics of Lys Succinylation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that SIRT5 is a central regulator of Lys succinylation in mammalian cells”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“SIRT5 promotes urea cycle function via the regulation of carbamoyl phosphate synthase (CPS1) (Nakagawa et al., 2009; Ogura et al., 2010)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > INTRODUCTION
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting differential regulation of succinylation and acetylation.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our analysis of Lys succinylation and acetylation in Sirt5 WT and KO cells suggests that there is a limited overlap between the two modifications, implying different regulatory mechanisms.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Elevated succinate levels can lead to epigenetic dysregulation (Cervera et al., 2009; Smith et al., 2007).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggested that SIRT5 negatively regulates PDC activity.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistent with a role for SIRT5 in regulating Ksucc levels extra-mitochondrially, we find that a substantial fraction of SIRT5 protein is cytosolic.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“a SIRT5H158Y mutant showed hypomorphic desuccinylase activity (Nakagawa et al., 2009).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
What the sources say
- Not checked yetcites Nakagawa et al., 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, SIRT5 could play a role in neoplasia by regulating PDC and SDH.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is in contrast to Lys acetylation, which primarily occupies the N-terminal tails of histones, potentially suggesting a distinct epigenetic role of histone Lys succinylation in comparison to Lys acetylation.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Lysine acetylation primarily localizes to the N-terminal tails of histones.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, it is likely that the impact of SIRT5 on mitochondrial respiration and overall metabolism is much broader than repressing PDC and SDH function.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 15
- It may state two separate claims as one. 26
Every source the paper cites for this claim was checked and supports it.
In the paper
“SIRT5 is thought to localize primarily to mitochondria (Lombard et al., 2007; Michishita et al., 2005; Nakagawa et al., 2009; Schlicker et al., 2008).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Cellular Localization of the Lys Succinylation Proteome
What the sources say
- Supportedcites Lombard et al., 2007 source
The Results report that SIRT5 was known to localize to mitochondria and identify SIRT5 protein in liver mitochondria, calling this the first demonstration of endogenous SIRT5 there. This supports the citing sentence’s hedged description of SIRT5 as primarily mitochondrial, although the paper does not quantify its distribution across compartments. (LLM, conf=0.86)
- Supportedcites Michishita et al., 2005 source
The Results section reports that tagged SIRT5 colocalized with mitochondrial markers in human cells and was found exclusively in the mitochondrial fraction of transfected cells. The Discussion likewise identifies SIRT5 as mitochondrial, supporting the citing sentence’s hedged localization claim. (LLM, conf=0.93)
- Supportedcites Nakagawa et al., 2009 source
The Results section, “SIRT5 is a broadly expressed mitochondrial protein,” reports clear localization of SIRT5 to the mitochondrial matrix in fractionated murine liver mitochondria and concludes that SIRT5 is a mitochondrial matrix protein. This supports the citing sentence’s more cautious localization claim. (LLM, conf=0.94)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Our previous studies identified Ksucc sites on E. coli IDH (Zhang et al., 2011).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
- Supportedcites Zhang et al., 2011 source
The Results section, “Sequence alignment and mutagenesis analysis,” identifies Lys100 and Lys242 as two succinylated lysine residues in isocitrate dehydrogenase. The Results section, “Confirmation of lysine succinylation using western blot,” specifies that the enzyme studied was from E. coli. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Lysine Succinylation Proteome in Mouse Cells
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Flanking Sequence and PTM Correlation Analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SIRT5 (green) partially colocalized with MitoTracker Red to produce a yellow signal. However, a detectable fraction of SIRT5 was present cytosolically”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Is Present Extramitochondrially
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Functional Annotation of the Lys Succinylome
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, SIRT5 is present both mitochondrially and extramitochondrially”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Is Present Extramitochondrially
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Protein Complex Analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: Core protein complexes are evolutionarily conserved among mammalian species.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Protein Interaction Networks of Lys Succinylation Proteome
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Cellular Localization of the Lys Succinylation Proteome
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“32% of the Ksucc sites had stoichiometries greater than 10% in Sirt5 WT cells, whereas this figure increased to 56% in Sirt5 KO cells”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Quantitative Analysis of Lys Succinylation and Acetylation Sites in Response to Sirt5 KO
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
- Not checked yetcites Xie et al., 2012 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This modification is widespread in fibroblasts and hepatocytes, occurring on both mitochondrial metabolic enzymes as well as extramitochondrial proteins such as histones and ribosomes.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“3-NPA treatment, but not malonate treatment or SDHC KD, resulted in a slight increase in Ksucc levels.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the modification of specific sites may occur much more rapidly.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > Kinetics of Lys Succinylation
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > INTRODUCTION
What the sources say
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § INTRODUCTION · hedged
In the paper
“Less is known regarding the functions of SIRT4 and SIRT5, which, unlike SIRT3, do not impact bulk mitochondrial protein acetylation (Lombard et al., 2007).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > INTRODUCTION
What the sources say
- Not checked yetcites Lombard et al., 2007 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“which stimulates PDC activity by reducing the phosphorylation and turnover of E1α (Morten et al., 1999; Stacpoole et al., 2008).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, mechanisms of Lys succinylation remain unclear.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Mutations in the IDH2 gene, a mammalian IDH homolog, causes D-2 hydroxyglutaric aciduria type 2 (D2HGA2) (Kranendijk et al., 2010)”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
- Not checked yetcites Kranendijk et al., 2010 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data imply that SIRT5 functions outside mitochondria, potentially impacting chromatin functions.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“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).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
- Not checked yetcites Selak et al., 2005 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, SIRT5 and E1α phosphorylation attenuate PDC activity through distinct mechanisms.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses Pyruvate Dehydrogenase Complex Activity
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest a potential impact of Lys succinylation on the activity of IDH2, which may impact epigenetic regulation and neoplasia.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § DISCUSSION · plain
In the paper
“whereas its downregulation leads to epigenetic dysfunction via the loss of 5-hydroxymethyl-cytosine in melanoma (Lian et al., 2012).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
- Not checked yetcites Lian et al., 2012 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“IDH1 or IDH2 mutations lead to production of the oncometabolite D2-hydroxyglutarate (D-2HG) (Yen et al., 2010).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
- Not checked yetcites Yen et al., 2010 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Germ-line mutations in all Sdh subunit genes can cause mitochondrial disease and tumor susceptibility syndromes (Gill, 2012).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > RESULTS > SIRT5 Suppresses SDH Activity and Cellular Respiration
What the sources say
- Not checked yetcites Gill, 2012 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“About 50% of overall daily caloric intake passes through PDC, highlighting the central importance of this holoenzyme in glucose metabolism (Patel and Korotchkina, 2006).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
- Not checked yetcites Patel and Korotchkina, 2006
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
- Not checked yetcites Patel and Korotchkina, 2006
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The regulation of PDC activity is the major mechanism regulating glucose oxidation in mammals in vivo (Wieland et al., 1972).”
§ SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways > DISCUSSION
What the sources say
- Not checked yetcites Wieland et al., 1972 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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”
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
“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
In the citing paper
“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
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
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Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206
KEGG: Kyoto Encyclopedia of Genes and Genomes
Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., & Kanehisa, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.29 · Cited by 31,232
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
The Pfam Protein Families Database
Bateman, A. G. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.276 · Cited by 14,075
An automated method for finding molecular complexes in large protein interaction networks
Bader, G. D., & Hogue, C. W. V. (2003) · BMC Bioinformatics · doi:10.1186/1471-2105-4-2 · Cited by 6,112
Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment
Cox, J., Neuhauser, N., Michalski, A., Scheltema, R. A., Olsen, J. V., & Mann, M. (2011) · Journal of Proteome Research · doi:10.1021/pr101065j · Cited by 5,520
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
Cited by
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The metabolic signature of macrophage responses
Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T., & Castegna, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01462 · Cited by 2,021
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
Metabolic regulation of gene expression through histone acylations
Sabari, B. R., Zhang, D., Allis, C. D., & Zhao, Y. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.140 · Cited by 1,168
Self-citationNAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W. Q., Huang, C., Huber, P., Zhou, X., Li, C. L., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,147
Mitochondrial dysfunction in cell senescence and aging
Miwa, S., Kashyap, S., Chini, E., & von Zglinicki, T. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158447 · Cited by 1,061
Metadata
- 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)
- 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
- bronze
- doi.org
- 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.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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.
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