The DOI matches its Crossref record; 103 of the 103 references it cites were found in a registry or an index; 6 of the 149 sources its claims cite were checked for support.
The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications
Open accessAbstract
Post-translational modification of lysine residues via reversible acylation occurs on proteins from diverse pathways, functions, and organisms. While nuclear protein acylation reflects the competing activities of enzymatic acyltransferases and deacylases, mitochondrial acylation appears to be driven mostly via a non-enzymatic mechanism. Three protein deacylases, SIRT3, SIRT4, and SIRT5, reside in the mitochondria and remove these modifications from targeted proteins in an NAD+-dependent manner. Recent proteomic surveys of mitochondrial protein acylation have identified the sites of protein acetylation, succinylation, glutarylation, and malonylation and their regulation by SIRT3 and SIRT5. Here, we review recent advances in this rapidly moving field, their biological significance, and their implications for mitochondrial function, metabolic regulation, and disease pathogenesis.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that mitochondrial lysine acylation is largely a non-enzymatic consequence of reactive acyl-CoA species and is reversed by mitochondrial sirtuins SIRT3, SIRT4, and SIRT5. It synthesizes proteomic and biochemical evidence linking these modifications to mitochondrial metabolism, stress responses, and diseases including metabolic syndrome, cancer, neurological disorders, and hearing loss.
Key findings
- Mitochondrial acylation includes acetylation, succinylation, malonylation, glutarylation, and other acyl marks; SIRT3 is the major mitochondrial deacetylase, SIRT5 removes acidic acyl groups such as succinyl, malonyl, and glutaryl, and SIRT4 remains the least understood but has been linked to lipoyl, biotinyl, and branched-chain acyl modifications.
- Proteomic surveys mapped thousands of sites: for example, 2,187 acetylation sites in 483 mouse liver mitochondrial proteins, with 283 sites in 136 proteins increased more than twofold in SIRT3-deficient mice; 2,565 succinylation sites in 779 proteins in SIRT5-deficient liver and MEFs; and 1,137 malonylation sites in 430 proteins, with 183 sites increased in SIRT5 knockout liver.
- Acylation is often inhibitory for mitochondrial enzymes, and sirtuin-mediated removal can activate pathways such as fatty acid oxidation, ketone body synthesis, the urea cycle, and oxidative stress defense; examples include PDH, HMGCS2, CPS1, OTC, MnSOD, and IDH2.
- Disease connections include SIRT3 loss with metabolic syndrome, pulmonary arterial hypertension, age-related hearing loss, and context-dependent cancer roles; SIRT5 loss with altered ketone body production, ammonia handling, and glycolysis; and SIRT4 with leucine metabolism and insulin secretion.
Methods
- Narrative review synthesizing published proteomic, biochemical, genetic, and structural studies; no new primary experimental data are reported.
- The paper compares mass-spectrometry strategies for acylation profiling, including label-free quantification, SILAC, isobaric tagging such as TMT, and newer stoichiometry methods.
- Evidence discussed comes from mouse knockout models, cell lines, human tissues, and in vitro enzyme assays, with emphasis on SIRT3 and SIRT5 datasets and selected SIRT4 studies.
Limitations
- Stated: SIRT4’s enzymatic activity and target specificity remain poorly defined; most acylation sites appear to have low stoichiometry, often below 1% for acetylation, raising questions about functional relevance; indirect SILAC-based stoichiometry can overestimate occupancy because lysine carries multiple modifications; and study discrepancies exist, such as the 28% versus 79% overlap reported between succinylation and acetylation sites.
- Stated: the mechanisms connecting acylation changes to whole-organism disease phenotypes are largely unknown, and many disease effects are likely mediated by multiple low-occupancy modifications rather than a single site.
- Evident: as a review, the conclusions depend on the cited literature rather than new experiments, and the field lacks comprehensive stoichiometry data for most acyl modifications.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
106 Not checked yet · 42 Own interpretation · 6 No basis given · 2 Supported · 1 Partly supported · 1 Mixed support · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“However, prolonged hypernutrition leads to type 2 diabetes, and has been shown to impair skeletal muscle glucose uptake in a manner exacerbated by the loss of SIRT3 (Jing et al. 2013),(Lantier et al. 2015).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Diet
What the sources say
- Disputedcites Jing et al. 2013 sourceExperimental — accuracy not yet measured
The Results (page unavailable) report reduced glucose oxidation in Sirt3-knockout muscle but say that unchanged glycolysis and normal insulin-responsive glycogen synthesis suggest glucose uptake was normal. The Methods (page unavailable) specify a standard-chow diet, not a hypernutrition intervention. The paper therefore does not show that Sirt3 loss exacerbates hypernutrition-induced impairment of glucose uptake. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
- Supportedcites Lantier et al. 2015 source
The Introduction reports that high-fat-fed SIRT3-knockout mice have exacerbated insulin resistance compared with wild-type littermates, due to defects in skeletal muscle metabolism. The Discussion states that insulin-stimulated muscle glucose uptake is markedly impaired in SIRT3-knockout mice under nutrient overload. The evidence is specific to high-fat-fed mice and insulin-stimulated uptake. (LLM, conf=0.93)
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.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“Mitochondrial hyperacetylation thus tends to limit the metabolic adaptations necessary for proper function during fasting; SIRT3 is upregulated during fasting to combat this process (Hirschey et al. 2010), and many mitochondrial proteins are hyperacetylated during fasting (Still et al. 2013).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Diet
What the sources say
- Supportedcites Still et al. 2013 source
In “Quantitative Analysis of Mitochondrial Acetylation Dynamics during Fasting and Refeeding,” the authors report that the vast majority of dynamic acetylation sites decreased in occupancy after refeeding. Their comparison of fasted and refed mouse liver mitochondria supports the attributed claim that many mitochondrial proteins are more highly acetylated during fasting; the passage does not supply a page number. (LLM, conf=0.93)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“SIRT3 knockout mice exhibit metabolic changes similar to those observed in the human metabolic syndrome ((Hirschey et al. 2011);(Jing et al. 2013)), and a human SIRT3 polymorphism associated with reduced SIRT3 deacetylase activity is associated with increased risk of metabolic syndrome in humans ((Hirschey et al. 2011).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Metabolic syndrome, obesity, and diabetes
What the sources say
- Supportedcites Hirschey et al. 2011 source
The Results sections on diet-induced obesity and insulin resistance and on hyperlipidemias report insulin resistance, elevated fasting insulin, and abnormal blood lipids in SIRT3 knockout mice—features the paper identifies with metabolic syndrome. These findings are reported particularly in older mice or those fed a high-fat diet; page numbers are not provided in our copy. (LLM, conf=0.92)
- Partly supportedcites Jing et al. 2013 sourceExperimental — accuracy not yet measured
The Results section on the altered metabolic profile reports a metabolic derangement in Sirt3-knockout mouse skeletal muscle, including reduced glucose oxidation and increased lipid use. The Discussion links Sirt3 to human metabolic syndrome, but our copy does not compare the knockout mice’s metabolic changes with those observed in people with the syndrome. No page numbers were provided in our copy. (LLM, conf=0.82)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“via identification of a SIRT3 polymorphism previously associated with metabolic syndrome ((Hirschey et al. 2011) in a cohort of 162 patients and controls.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Pulmonary Arterial Hypertension
What the sources say
- Supportedcites Hirschey et al. 2011 source
The Results section reports that SIRT3 SNPs were associated with metabolic syndrome, supporting the prior association attributed to Hirschey et al. The citation is attached to that association; the 162-patient-and-control cohort describes the citing study, not Hirschey et al.’s cohort, which comprised 834 DNA samples. (LLM, conf=0.91)
plaincorrelationaln = 162- 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.
- Supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Three protein deacylases, SIRT3, SIRT4 and SIRT5 reside in the mitochondria and remove these modifications from targeted proteins in an NAD+-dependent manner.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Abstract
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.
In the paper
“Early experiments using western blotting analysis and antisera specific for acetyl-lysine showed globally increased mitochondrial protein acetylation in mice lacking SIRT3 ((Lombard et al. 2007)), indicating that SIRT3 was the major mitochondrial protein deacetylase.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial sirtuins: SIRT3, SIRT4 and SIRT5 are protein deacylases
What the sources say
- Not checked yetcites Lombard et al. 2007 source
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.
In the paper
“Similarly, and from the same study, human SCAD-deficient fibroblasts show increased lysine butyrylation, patients with malonyl-CoA decarboxylase (MCD) deficiency exhibit increased protein malonylation and finally, propionyl-CoA carboxylase (PCC) deficient patient cells show increased lysine propionylation.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Local acyl-CoA concentrations and molecular context
What the sources say
- Not checked yetcites Pougovkina et al. 2014 source
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.
In the paper
“Loss of SIRT3 has been shown to inhibit fatty acid oxidation ((Hirschey et al. 2010)); the same study showed decreased gluconeogenic production of glucose in response to cold challenge and decreased production of the ketone body beta-hydroxybutyrate during fasting.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Diet
What the sources say
- Not checked yetcites Hirschey et al. 2010 source
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
“This redox-sensitive mechanism means that certain acetylation sites observed in mitochondria may be regulated by glutathione redox balance and glyoxalase II in addition to mitochondrial sirtuins.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > How does mitochondrial protein acylation occur?
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
“This mechanism has been shown to affect both acetylation and succinylation; other acylation modifications are likely to be similarly affected.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > How does mitochondrial protein acylation occur?
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.
- It may state two separate claims as one. 60
- Probably not a substantial claim. 6
None of the sources cited for this claim have been checked yet.
In the paper
“One study has shown that SIRT4 can regulate the levels of both lipoyl- and biotinyl-lysine modifications in pyruvate dehydrogenase and likely other proteins ((Mathias et al. 2014)).”
- Also stated in: § The Emerging Targets of SIRT4 · plain
“Recombinant SIRT4 was sufficient to demethylglutarylate lysine residues, and SIRT4-overexpressing cells contained lower levels of these branched-chain acyl-lysines.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > The Emerging Targets of SIRT4
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.
It may state two separate claims as one.
- Also stated in: § The Emerging Targets of SIRT4 · plain
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
“While nuclear protein acylation reflects the competing activities of enzymatic acyltransferases and deacylases, mitochondrial acylation appears to be driven mostly via a non-enzymatic mechanism.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Abstract
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
“This work resulted in the identification of novel modifications targeted by SIRT5: succinylation, malonylation and glutarylation as described in details below ((Du et al. 2011{Zhang, 2011 #16);(Peng et al. 2011);(Tan et al. 2014)}.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial sirtuins: SIRT3, SIRT4 and SIRT5 are protein deacylases
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.
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
“Assuming that ACAT1 is capable of holding a reactive acetyl-CoA molecule in place for long enough, increasing the local concentration of reactive thioester, a semi-enzymatic mechanism may account for increased acetylation to PDP1/PDHA1.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > How does mitochondrial protein acylation occur? > Mitochondrial Acyltransferases: enzymatic and pseudo-enzymatic acylation?
hedgedconditional- 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: ACAT1 can hold a reactive acetyl-CoA molecule in place long enough to increase the local concentration of reactive thioester, enabling a semi-enzymatic mechanism for increased acetylation of PDP1 and PDHA1.
In the paper
“GCN5L1 interacts with and promotes acetylation respiratory chain target proteins and reverses global SIRT3 effects on mitochondrial protein acetylation, respiration and bioenergetics ((Scott et al. 2012)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > How does mitochondrial protein acylation occur? > Mitochondrial Acyltransferases: enzymatic and pseudo-enzymatic acylation?
What the sources say
- Not checked yetcites Scott et al. 2012 source
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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Recent proteomic surveys of mitochondrial protein acylation have identified the sites of protein acetylation, succinylation, glutarylation and malonylation and their regulation by SIRT3 and SIRT5.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Abstract
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
“For example, denatured proteins are more rapidly acetylated by coincubation with acetyl-CoA (Wagner and Payne 2013), indicating that local structure slows acylation; past studies have shown that sirtuins favor either unstructured regions (Khan and Lewis 2005, Smith et al. 2011) or, in the case of SIRT3, beta sheets (Smith et al. 2011).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Local acyl-CoA concentrations and molecular context
What the sources say
- Not checked yetcites Wagner and Payne 2013
hedgeddirect- 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
“Broadly, dietary inputs and the metabolic demands of various tissues create acyl-CoA concentrations with interact with molecular contexts in mitochondria to drive acylation at differing rates for different targets; gene expression of and NAD+ supply to sirtuins then reverses this process.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation
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: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Voltage-dependent anion channels (VDACs) are outer mitochondrial membrane proteins with tissue-dependent expression patterns and are part of the acylcarnitine translocase pathway ((Lee, Kerner, and Hoppel 2011)); their partners on the inner membrane, adenine nucleotide translocases (ANTs), are known to be acetylated and some sites are predicted to be functionally important to channel function (Mie”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Local acyl-CoA concentrations and molecular context
What the sources say
- Not checked yetcites Lee, Kerner, and Hoppel 2011 source
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.
In the paper
“Mice with short-chain acyl-CoA dehydrogenase (SCAD) deficiency accumulate high levels of butyryl-CoA and show increased protein lysine butyrylation ((Pougovkina et al. 2014)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Local acyl-CoA concentrations and molecular context
What the sources say
- Not checked yetcites Pougovkina et al. 2014 source
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.
In the paper
“Genetic knockdown of GCN5L1 blunts mitochondrial protein acetylation, and its reconstitution in intact mitochondria restores protein acetylation.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > How does mitochondrial protein acylation occur? > Mitochondrial Acyltransferases: enzymatic and pseudo-enzymatic acylation?
What the sources say
- Not checked yetcites Scott et al. 2012 source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“However, prolonged hypernutrition leads to type 2 diabetes, and has been shown to impair skeletal muscle glucose uptake in a manner exacerbated by the loss of SIRT3 (Jing et al. 2013),(Lantier et al. 2015).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Diet
What the sources say
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.
In the paper
“Metabolic supplier organs such as the liver and kidney demonstrate mitochondrial hyperacetylation under CR, as does the heart (Schwer et al. 2009); brain mitochondrial acetylation was unchanged, however, and skeletal muscle acetylation decreased.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Diet
What the sources say
- Not checked yetcites Schwer 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.
It may state two separate claims as one.
In the paper
“Loss of SIRT3 has been shown to inhibit fatty acid oxidation ((Hirschey et al. 2010)); the same study showed decreased gluconeogenic production of glucose in response to cold challenge and decreased production of the ketone body beta-hydroxybutyrate during fasting.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Diet
What the sources say
- Not checked yetcites Hirschey et al. 2010 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.
In the paper
“Proteomic characterization of the changes in liver reveals a complicated landscape of alterations, but an overall increase in acetylation levels for mitochondrial proteins but not those found in other cellular compartments during CR (Hebert et al. 2013).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Diet
What the sources say
- Not checked yetcites Hebert et al. 2013 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.
In the paper
“their partners on the inner membrane, adenine nucleotide translocases (ANTs), are known to be acetylated and some sites are predicted to be functionally important to channel function (Mielke et al. 2014).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Local acyl-CoA concentrations and molecular context
What the sources say
- Not checked yetcites Mielke et al. 2014 source
boosted- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“past studies have shown that sirtuins favor either unstructured regions (Khan and Lewis 2005, Smith et al. 2011) or, in the case of SIRT3, beta sheets (Smith et al. 2011).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Local acyl-CoA concentrations and molecular context
What the sources say
- Not checked yetcites Khan and Lewis 2005
- Not checked yetcites Smith et al. 2011 source
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 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
“As NAD+ supplementation also results in potentially beneficial production of N-methylnicotinamide via sirtuins ((Schmeisser et al. 2013)), evidence such as the link to MnSOD affirms roles for acylation both as a direct effector modulated by NAD+ and in transducing NAD+ into an N-methylnicotinamide signal.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > NAD+ Availability
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
“First, SIRT3 deacetylates K321 and second, SIRT3 also deacetylates PDP, enhancing its phosphatase activity on PDC and thereby decreasing PDC phosphorylation. ((Fan et al. 2014)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Pyruvate dehydrogenase
What the sources say
- Not checked yetcites Fan et al. 2014 source
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
“Lipoylation occurs at two sites in the E2 N-terminal region (K132 and K259 in the human sequence), and is enzymatically reversed by SIRT4 ((Mathias et al. 2014)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Pyruvate dehydrogenase
What the sources say
- Not checked yetcites Mathias et al. 2014 source
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
“The effect of SIRT5-mediated removal of PDC succinylation is not known but would be expected to activate the enzyme similar to SIRT3.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Pyruvate dehydrogenase
hedgedconditional- 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. It may state two separate claims as one.
In the paper
“Acetylation of PDHA1 K321 recruits PDK leading to PDC phosphorylation and inhibition of its enzymatic activity.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Pyruvate dehydrogenase
What the sources say
- Not checked yetcites Jing et al. 2013 source
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
“These effects appear to be mediated in the mitochondria because SIRT3-overexpressing mice are resistant to noise-induced hearing loss and SIRT3 deletion abrogates the protective effects of nicotinamide riboside ((Brown et al. 2014))”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > NAD+ Availability
What the sources say
- Not checked yetcites Brown et al. 2014 source
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.
In the paper
“Lysine succinylation has been observed on DLAT in addition to DLD and PDHA1, including multiple succinylations controlled by SIRT5 ((Rardin, He, et al. 2013)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Pyruvate dehydrogenase
What the sources say
- Not checked yetcites Rardin, He, et al. 2013
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
“SIRT3 therefore facilitates the catabolism of fatty acids in the liver and the peripheral use of lipid-derived acetate and ketone bodies during fasting.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Lipid Metabolism
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
“For example, lysine residues near arginine may have decreased pKa and be more likely to have no charge, leaving their free electron pair available for acylation.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > Local acyl-CoA concentrations and molecular context
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.
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, SIRT3 and SIRT4 regulate the PDC in opposing directions; SIRT3’s clearance of lysine acetylation allows for efficient PDC function, while SIRT4’s removal of enzymatically active cofactors from specific lysine residues inhibits the PDC.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Pyruvate dehydrogenase
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
“Administering the NAD precursor nicotinamide riboside prevents noise-induced hearing loss and degeneration of spiral ganglia neurite degeneration.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Regulation of mitochondrial protein acylation > NAD+ Availability
What the sources say
- Not checked yetcites Brown et al. 2014 source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“SIRT3 and SIRT5 both positively regulate HMGCS2 activity via respectively deacetylating and desuccinylating it ((Shimazu et al. 2010))((Rardin, He, et al. 2013)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Ketone body synthesis
What the sources say
- Not checked yetcites Shimazu et al. 2010 source
- Not checked yetcites Rardin, He, et al. 2013
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Mice lacking SIRT5 fail to upregulate CPS1 activity and show elevated blood ammonia under these conditions ((Nakagawa et al. 2009))((Tan et al. 2014)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Urea Cycle
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“At least 52 lysine sites are found to be acetylated, 44 sites succinylated, 33 sites glutarylated and 29 sites malonylated.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Urea Cycle
What the sources say
- Not checked yetcites Nakagawa et al. 2009 source
- Not checked yetcites Rardin, Newman, et al. 2013
- Not checked yetcites Rardin, He, et al. 2013
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 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
“The two mitochondrial enzymes, carbamoyl phosphate synthetase 1 (CPS1) and Ornithine transcarbamylase (OTC), which carry out the first two steps of urea cycle reactions, are both regulated by the activities of mitochondrial sirtuins.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Urea Cycle
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
“Calorie restriction stimulates the urea cycle and up-regulates OTC activity; this up-regulation of OTC activity is lost in the absence of SIRT3, leading to increased orotic acid levels, a known outcome of OTC deficiency ((Hallows et al. 2011)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Urea Cycle
What the sources say
- Not checked yetcites Hallows et al. 2011 source
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
“SIRT5, by removing these succinyl groups, restores the positively charged microenvironment and facilitates enzymatic function.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Ketone body synthesis
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
“Beta-hydroxybutyrate is an endogenous inhibitor of HDACs and can thereby affect gene expression via chromatin modifications and regulate the response to oxidative stress ((Shimazu et al. 2013)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Ketone body synthesis
What the sources say
- Not checked yetcites Shimazu et al. 2013 source
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
“Structural simulations show that in silico deacetylation of these three lysines causes conformational changes of HMGCS2 near the catalytic site, suggesting acetylation might interfere with the enzymatic activity via changing its conformation ((Shimazu et al. 2010)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Ketone body synthesis
What the sources say
- Not checked yetcites Shimazu et al. 2010 source
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
“This highly positive microenvironment might be disrupted when the two lysines are modified by negatively charged succinyl groups leading to a reduction in enzymatic activity.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Ketone body synthesis
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
“Mice lacking SIRT3 or SIRT5 have reduced levels of ketone bodies upon fasting, supporting a positive role for sirtuins in regulating ketone body biosynthesis ((Shimazu et al. 2010))((Rardin, He, et al. 2013)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Ketone body synthesis
What the sources say
- Not checked yetcites Shimazu et al. 2010 source
- Not checked yetcites Rardin, He, et al. 2013
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
“The three other enzymes in the urea cycle are located in the cytosol and are also malonylated at multiple sites with demalonylation at some sites by SIRT5 (Nishida et al. 2015).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Urea Cycle
What the sources say
- Not checked yetcites Nishida et al. 2015 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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“CPS1 is the most heavily modified protein in mitochondria, possibly due to its high abundance and relatively large size.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Urea Cycle
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The mitochondrial SIRT3 deacetylates two of these enzymes: manganese superoxide dismutase (MnSOD) (Tao et al. 2010) and isocitrate dehydrogenase 2 (IDH2)(Someya et al. 2010).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Oxidative Stress
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Similarly, SIRT3 function has been shown to attenuate cell death after excitotoxic stress, and mediates the protective effect of exercise against such stress ((Cheng et al. 2016)), possibly via deacetylation of cyclophilin D ((Cheng et al. 2016),(Amigo et al. 2017)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Neurological Disease
What the sources say
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both MnSOD and the various mitochondrial superoxide sources are acylated ((Rardin, Newman, et al. 2013), (Rardin, He, et al. 2013);(Tan et al. 2014)); MnSOD also carries glutarylation, succinylation, and acetylation at functionally required lysine residues near its active site, K122 in particular bears all three modifications ((Tao et al. 2010)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Oxidative Stress
What the sources say
- Not checked yetcites Rardin, Newman, et al. 2013
- Not checked yetcites Rardin, He, et al. 2013
- Not checked yetcites Tan et al. 2014 source
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 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
“SIRT4 control of tumorigenesis is therefore particularly relevant to c-Myc-driven, mitochondrially active, glutamine-dependent tumors, while SIRT3 prevents less mitochondrially active tumors.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Cancer
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.
None of the sources cited for this claim have been checked yet.
In the paper
“GLUD1 is inhibited by SIRT4 ((Haigis et al. 2006)) and by acetylation which can be reversed by SIRT3 ((Schlicker et al. 2008)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Oxidative Stress
What the sources say
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.
In the paper
“Oxidized glutathione thus underpins all mitochondrial H2O2 detoxification, and is reduced by NADPH-dependent glutathione reductases ((Merksamer et al. 2013)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Oxidative Stress
What the sources say
- Not checked yetcites Merksamer et al. 2013 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
“Given the effects already demonstrated of mitochondrial acylation in allowing tumorigenesis and increasing production of reactive oxygen species, it should come as no surprise that mitochondrial acylation can modulate neuronal function - and, more interestingly, that its removal by sirtuins can help improve health.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Neurological Disease
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
“IDH2 function is inhibited by acetylation, and its deacetylation by SIRT3 restores function ((Schlicker et al. 2008)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Oxidative Stress
What the sources say
- Not checked yetcites Schlicker et al. 2008 source
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
“These are argininosuccinate synthase (ASSY), argininosuccinate lyase (ARLY), and arginase (ARGI1); ASSY is demalonylated by SIRT5 at 2 of 11, ARLY at 1 of 6, and ARG1 at 3 of 16 malonyllysine sites.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Urea Cycle
What the sources say
- Not checked yetcites Nishida et al. 2015 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.
None of the sources cited for this claim have been checked yet.
In the paper
“SIRT3 has been reported as pro-apoptotic ((Allison and Milner 2007)) and SIRT3 loss is associated with a tumor-permissive environment via the inhibition of ROS production ((Kim et al. 2010);(Bell et al. 2011);(Finley et al. 2011)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Cancer
What the sources say
hedgedcorrelational- 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
“MnSOD also carries glutarylation, succinylation, and acetylation at functionally required lysine residues near its active site, K122 in particular bears all three modifications ((Tao et al. 2010)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Oxidative Stress
What the sources say
- Not checked yetcites Tao et al. 2010 source
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 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
“IDH2 competes with NAD+-dependent IDH3 for isocitrate; tuning the activity of IDH2 thus regulates available NADPH for H2O2 detoxification.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Oxidative Stress
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
“thiol residues are as capable as deprotonated amines of mediating nucleophilic attack, if not more so, and are found in large numbers in the mitochondrial matrix ((Requejo et al. 2010)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Where Does Acylation Go from Here?
What the sources say
- Not checked yetcites Requejo et al. 2010 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 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
“Given that studies often find pathway-wide acylation, it may be that the cumulative effect of dozens of low-occupancy modifications mediates biological effects.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Where Does Acylation Go from Here?
hedgedconditional- 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
“Loss of SIRT3 activity thus limits the functional envelope of mitochondria in multiple directions, with the precise failure mechanism for a given disease depending on which of many connected mitochondrial pathways is most taxed and thus most sensitive to hyperacetylation.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Pulmonary Arterial Hypertension
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
“SIRT3 thus fights aging by attenuating the development of systemic stressors such as NAD+ loss and by enhancing our ability to survive the resulting insults.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Aging
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
“The V208I mutation caused by this polymorphism both increased the KM of SIRT3 for NAD+ and reduced the Vmax of the enzyme towards peptide substrate, reducing overall catalytic efficiency and mimicking the effects of reduced SIRT3 expression at the whole-body level and creating a ~1.4-fold increase in risk for metabolic syndrome ((Hirschey et al. 2011)).”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Metabolic syndrome, obesity, and diabetes
What the sources say
- Not checked yetcites Hirschey et al. 2011 source
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
“while sirtuins may not alter the overall rate of organismal aging”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Aging
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.
In the paper
“These effects are dependent on SIRT3, since SIRT3-overexpressing mice are resistant to noise-induced hearing loss and SIRT3 deletion abrogates the protective effects of NR.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Age- and noise-associated hearing loss
What the sources say
- Not checked yetcites Brown et al. 2014 source
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
“Current research argues both for and against a causative role for mitochondrial protein acylation in metabolic disorders.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Metabolic syndrome, obesity, and diabetes
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.
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
“Hypernutrition and its associated disease states, such as obesity and type 2 diabetes, are characterized by an increased availability of the acyl-CoA precursors which are believed to drive the bulk of mitochondrial acylation.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Metabolic syndrome, obesity, and diabetes
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Cochlear NAD(+) levels increased in mice after administering nicotinamide riboside, a precursor to NAD(+) and prevented noise-induced hearing loss.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Age- and noise-associated hearing loss
What the sources say
- Not checked yetcites Brown et al. 2014 source
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
“The CD38-induced loss of NAD+ with age thus leads to increases in inflammatory SASP cytokines, which in turn lead to proliferation of CD38-expressing cells; SIRT3 function, by attenuating the resulting loss of mitochondrial function, helps keep this loop in check.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Aging
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
“Increased acetylation of mitochondrial proteins in the affected smooth muscle leads to mitochondrial hyperpolarization, increased proliferation, suppressed apoptosis, and eventually to progressive arterial thickening.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Pulmonary Arterial Hypertension
What the sources say
- Not checked yetcites Paulin et al. 2014 source
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
“the same polymorphism can lead to pathological gain of function in arterial cells and pathological loss of function in metabolism.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Pulmonary Arterial Hypertension
plainconditional- 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.
ACAT1 can hold a reactive acetyl-CoA molecule in place long enough to increase the local concentration of reactive thioester, enabling a semi-enzymatic mechanism for increased acetylation of PDP1 and PDHA1.
“Assuming that ACAT1 is capable of holding a reactive acetyl-CoA molecule in place for long enough, increasing the local concentration of reactive thioester, a semi-enzymatic mechanism may account for increased acetylation to PDP1/PDHA1.”
The paper relies on this without support.
Mitochondrial acylation sites generally have low stoichiometry.
“Given the generally low stoichiometry of mitochondrial acylation sites, each disease is likely mediated by multiple presently-unidentified acylations, each slightly but cooperatively impairing mitochondrial function.”
The paper relies on this without support.
Both over-nutrition and under-nutrition create abnormal metabolic states with high levels of acyl-CoAs.
“Both over- and under-nutrition create abnormal metabolic states with high levels of acyl-CoAs.”
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
“Since their discovery, the sirtuins have received much attention because they regulate key metabolic processes, stress responses and ageing biology7.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [7]
In the citing paper
“Specifically, recent evidence has shown that nuclear SIRT1, SIRT6 and SIRT7 are critical regulators of DNA repair and genome stability and that mitochondrial SIRT3, SIRT4 and SIRT5 and nuclear SIRT1 regulate mitochondrial homeostasis and metabolism7.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [7]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“identified 1137 unique malonylation sites in 430 total proteins of which 183 sites (13%) were increased”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > The acidic acyl modifications, lysine succinylation, malonylation and glutarylation are regulated by SIRT5
Reported 13 · recomputed 16.094987
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial protein acetylation is regulated by SIRT3
“Overall, they identified 6286 sites of acetylation, quantified the abundance of 80% of these sites in all five tissues”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial protein acetylation is regulated by SIRT3
“found a relatively small set of 87 shared sites, with a much larger number of sites unique to each tissue”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Cancer
“SIRT3 loss is associated with a tumor-permissive environment via the inhibition of ROS production”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the top down: System-wide effects in disease and in health > Cancer
“SIRT3’s attenuation of reactive oxygen species production appears to inhibit a glycolytic shift in potentially cancerous cells”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial protein acetylation is regulated by SIRT3
“including acetylation of K336 in PDH E1alpha subunit leading to inhibition of pyruvate dehydrogenase activity.”
§ The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, Metabolic and Disease Implications > Mitochondrial acylation from the bottom up: From individual targets to biological effects > Pyruvate dehydrogenase
“a functional role for acetylation has only been demonstrated for modification of lysine 321 of PDHA1”
Citations
Cites
Ong, S.-E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., & Mann, M. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m200025-mcp200 · Cited by 5,574
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
Regulation of cellular metabolism by protein lysine acetylation
Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., et al. (2010) · Science · doi:10.1126/science.1179689 · Cited by 1,910
Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor
Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., et al. (2013) · Science · doi:10.1126/science.1227166 · Cited by 1,777
Self-citationSIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., et al. (2010) · Nature · doi:10.1038/nature08778 · Cited by 1,687
Self-citationQuantitative Phosphoproteomics Reveals Widespread Full Phosphorylation Site Occupancy During Mitosis
Olsen, J. V., Vermeulen, M., Santamaría, A., Kumar, C., Miller, M. L., Jensen, L. J., Gnad, F., Cox, J., Jensen, T. S., Nigg, E. A., et al. (2010) · Science Signaling · doi:10.1126/scisignal.2000475 · Cited by 1,510
Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey
Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.026 · Cited by 1,487
Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase
Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J. H., Choi, B. H., et al. (2011) · Science · doi:10.1126/science.1207861 · Cited by 1,429
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S.-I. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.014 · Cited by 1,340
The growing landscape of lysine acetylation links metabolism and cell signalling
Choudhary, C., Weinert, B. T., Nishida, Y., Verdin, E., & Mann, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3841 · Cited by 1,324
Self-citation
Cited by
Sorted by citations
NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617
Self-citationFrom discoveries in ageing research to therapeutics for healthy ageing
Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019) · Nature · doi:10.1038/s41586-019-1365-2 · Cited by 1,389
Self-citationFunctions and mechanisms of non-histone protein acetylation
Narita, T., Weinert, B. T., & Choudhary, C. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0081-3 · Cited by 1,232
NAD+ 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 pathophysiology of heart failure
Zhou, B., & Tian, R. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120849 · Cited by 973
Metadata
- Authors
- Carrico, C., Meyer, J. G., He, W., Gibson, B. W., & Verdin, E.
- Affiliations
- Gladstone Institutes (US)
- Buck Institute for Research on Aging (US)
- Corresponding author
- Verdin, Eric
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 27
- Issue
- 3
- Pages
- 497-512
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5863732
- OpenAlex
- W2793563787
- Cited by
- 331
- References
- 103
- Citations by year
- 2026: 26 · 2025: 42 · 2024: 36 · 2023: 46 · 2022: 49 · 2021: 47 · 2020: 38 · 2019: 32 · 2018: 15
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIDDK (R24 DK085610)
- NIH (T32 AG000266)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- protein acetylation, succinylation, SIRT3, SIRT5, mitochondrial function, metabolic regulation, mitochondrial disease
- MeSH terms
- Acetylation, Acylation, Animals, Humans, Mitochondria, Protein Processing, Post-Translational, Mitochondrial Proteins, Sirtuins, Proteomics
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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