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DataSet Summary

  • HostingRepository: PRIDE
  • AnnounceDate: 2018-05-16
  • AnnouncementXML: Submission_2018-05-22_05:46:15.xml
  • DigitalObjectIdentifier:
  • ReviewLevel: Peer-reviewed dataset
  • DatasetOrigin: Original data
  • RepositorySupport: Unsupported dataset by repository
  • PrimarySubmitter: Paul Grimsrud
  • Title: Ablation of Sirtuin5 in the postnatal mouse heart results in persistent accumulation of protein succinylation and normal survival in response to chronic pressure overload
  • Description: Mitochondrial Sirtuin 5 (SIRT5) is an NAD+-dependent demalonylase, desuccinylase, and deglutarylase that controls several metabolic pathways. A number of recent studies point to SIRT5 desuccinylase activity being important in maintaining cardiac function and metabolism under stress. Previously, we described a phenotype of increased mortality in whole-body SIRT5KO mice exposed to chronic pressure overload compared to their littermate WT controls. We developed a tamoxifen-inducible, heart-specific SIRT5KO mouse model to determine if the survival phenotype we reported was due to a cardiac-intrinsic or cardiac-extrinsic effect of SIRT5. We discovered that postnatal cardiac ablation of Sirt5 resulted in persistent accumulation of protein succinylation up to 30 weeks after SIRT5 depletion. Succinyl proteomics revealed that succinylation increased on proteins of oxidative metabolism between 15 and 31 weeks post ablation. Heart-specific SIRT5KO mice were exposed to chronic pressure overload to induce cardiac hypertrophy. We found that, in contrast to whole-body SIRT5KO mice, there was no difference in survival between heart-specific SIRT5KO mice and their littermate controls. Overall, the data presented here suggest that survival in SIRT5KO mice may be dictated by a multi-tissue or prenatal effect of SIRT5.
  • SpeciesList: scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
  • ModificationList: N6-succinyl-L-lysine
  • Instrument: Q Exactive

Dataset History

VersionDatetimeStatusChangeLog Entry
02018-01-22 01:28:50ID requested
12018-05-16 02:09:45announced
22018-05-22 05:46:17announcedUpdated publication reference for PubMed record(s): 29769314.

Publication List

  1. Hershberger KA, Abraham DM, Liu J, Locasale JW, Grimsrud PA, Hirschey MD, in the postnatal mouse heart results in protein succinylation and normal survival in response to chronic pressure overload. J Biol Chem, 293(27):10630-10645(2018) [pubmed]

Keyword List

  1. curator keyword: Biological
  2. submitter keyword: Sirt5, protein succinylation, heart function

Contact List

    Matthew D. Hirschey
    • contact affiliation: Associate Professor, Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition, Department of Pharmacology and Cancer Biology Duke University Medical Center
    • contact email: matthew.hirschey@duke.edu
    • lab head:
    Paul Grimsrud
    • contact affiliation: Duke Molecular Physiology Institute
    • contact email: paul.grimsrud@duke.edu
    • dataset submitter:

Full Dataset Link List

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  2. PRIDE project URI
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