Evidence map›Paper›PMID 25505263›Full record

ArticleThe Journal of biological chemistry2015

Prolonged fasting identifies heat shock protein 10 as a Sirtuin 3 substrate: elucidating a new mechanism linking mitochondrial protein acetylation to fatty acid oxidation enzyme folding and function.

Zhongping Lu, Yong Chen, Angel M Aponte, Valentina Battaglia, Marjan Gucek, Michael N Sack

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.7field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
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  6. Review
  7. Mitochondrial unfolded protein response (UPRFrontiers in cell and developmental biology · 2024
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. HSP60 Regulates Lipid Metabolism in Human Ovarian Cancer.Oxidative medicine and cellular longevity · 2021
    Article
  16. Review
  17. Article
  18. Review
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  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Zhongping LuFrom the Cardiovascular and Pulmonary Branch and the Department of Biochemistry and Molecular Medicine, George Washington University, Washington, D. C. 20052, and the Veterans Affairs Medical Center, Washington, D. C. 20422 luz@gwu.edu.
Yong ChenProteomic Core Facility, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
Angel M AponteProteomic Core Facility, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
Valentina Battagliathe Department of Biochemistry and Molecular Medicine, George Washington University, Washington, D. C. 20052, and the Veterans Affairs Medical Center, Washington, D. C. 20422.
Marjan GucekProteomic Core Facility, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
Michael N SackFrom the Cardiovascular and Pulmonary Branch and sackm@nih.gov.
George Washington University · USNational Institutes of Health · USNational Heart Lung and Blood Institute · US

Funding

NHLBI Animal Program DivisionZIGHL006020 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI CLARK, TANNIA · 2009 to 2025
$47.3M
Proteomics CoreZICHL005903 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI GUCEK, MARJAN · 2009 to 2022
$23.3M
Role of intracellular organelle homeostasis in adaptation to dietary restrictive interventionsZIAHL006047 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI SACK, MICHAEL · 2010 to 2025
$15.6M
Mitochondrial Acetylation Modification in Regulating Drug-Induced Liver K22HL109236 · NHLBI · GEORGE WASHINGTON UNIVERSITY · PI LU, ZHONGPING · 2013 to 2015
$746k
NHLBI NIH HHS HL006047-01NHLBI NIH HHS K22 HL109236NHLBI NIH HHS K22HL109236
6 · The paper itself

Abstract

Although Sirtuin 3 (SIRT3), a mitochondrially enriched deacetylase and activator of fat oxidation, is down-regulated in response to high fat feeding, the rate of fatty acid oxidation and mitochondrial protein acetylation are invariably enhanced in this dietary milieu. These paradoxical data implicate that additional acetylation modification-dependent levels of regulation may be operational under nutrient excess conditions. Because the heat shock protein (Hsp) Hsp10-Hsp60 chaperone complex mediates folding of the fatty acid oxidation enzyme medium-chain acyl-CoA dehydrogenase, we tested whether acetylation-dependent mitochondrial protein folding contributes to this regulatory discrepancy. We demonstrate that Hsp10 is a functional SIRT3 substrate and that, in response to prolonged fasting, SIRT3 levels modulate mitochondrial protein folding. Acetyl mutagenesis of Hsp10 lysine 56 alters Hsp10-Hsp60 binding, conformation, and protein folding. Consistent with Hsp10-Hsp60 regulation of fatty acid oxidation enzyme integrity, medium-chain acyl-CoA dehydrogenase activity and fat oxidation are elevated by Hsp10 acetylation. These data identify acetyl modification of Hsp10 as a nutrient-sensing regulatory node controlling mitochondrial protein folding and metabolic function.

Indexed as

FastingProtein FoldingAcetylationAnimalsChaperonin 10Chromatography, GelElectrophoresis, Gel, Two-DimensionalFatty AcidsFlow CytometryGene Expression RegulationMiceMice, KnockoutMitochondriaMitochondrial ProteinsMolecular ChaperonesMutagenesisChaperonin 10Fatty AcidsMitochondrial ProteinsMolecular ChaperonesOxygenReactive Oxygen SpeciesSirt3 protein, mouseSirtuin 3Fatty Acid OxidationHeat Shock Protein (HSP)MitochondriaProtein FoldingSIRT3Sirtuin

Identifiers

PMID25505263
PMCPMC4303695
OpenAlexW2026859489

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.