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PXD011375

DataSet Summary

  • HostingRepository: jPOST
  • AnnounceDate: 2019-02-07
  • AnnouncementXML: Submission_2019-02-07_05:59:52.xml
  • DigitalObjectIdentifier:
  • ReviewLevel: Peer-reviewed dataset
  • DatasetOrigin: Original data
  • RepositorySupport: Unsupported dataset by repository
  • PrimarySubmitter: Paul Grimsrud
  • Title: Comprehensive respiratory phenomics across multiple models of mitochondrial protein hyperacylation reveals a paradoxically marginal impact on bioenergetics
  • Description: Acyl CoA metabolites derived from catabolism of carbon fuels can react with lysine residues of mitochondrial proteins, giving rise to a large family of post-translation modifications (PTMs). Mass spectrometry-based detection of thousands of acyl-PTMs scattered throughout the proteome has established a strong correlative connection between mitochondrial hyperacylation and disease; however, the functional consequences of these modifications remain uncertain. Here, we used a comprehensive respiratory diagnostics platform to evaluate three disparate mouse models of mitochondrial hyperacylation in heart caused by genetic deletion of malonyl CoA decarboxylase (MCD), the SIRT5 demalonylase/desuccinylase, or the SIRT3 deacetylase. In each case, elevated acylation was accompanied by surprisingly marginal respiratory phenotypes. Of the >30 mitochondrial energy fluxes evaluated, the only outcome observed consistently across models was ~15% decrease in ATP synthase activity. In sum, the findings suggest that the vast majority of mitochondrial acyl PTMs occur as stochastic events that have minimal impact on mitochondrial bioenergetics. See Fisher-Wellman et. al. 2018 for further experimental details, reagents, and references.
  • SpeciesList: scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
  • ModificationList: S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; MT6plex reporter+balance reagent N-acylated residue; N6-malonyl-L-lysine
  • Instrument: Q Exactive

Dataset History

VersionDatetimeStatusChangeLog Entry
02018-10-16 06:45:57ID requested
12019-02-07 05:59:53announced

Publication List

  1. Fisher-Wellman KH, Draper JA, Davidson MT, Williams AS, Narowski TM, Slentz DH, Ilkayeva OR, Stevens RD, Wagner GR, Najjar R, Hirschey MD, Thompson JW, Olson DP, Kelly DP, Koves TR, Grimsrud PA, Muoio DM, Respiratory Phenomics across Multiple Models of Protein Hyperacylation in Cardiac Mitochondria Reveals a Marginal Impact on Bioenergetics. Cell Rep, 26(6):1557-1572.e8(2019) [pubmed]

Keyword List

  1. submitter keyword: Protein Malonylation, Mitochondrial Bioenergetics, Complex V, ATP Synthase

Contact List

    Deborah M. Muoio
    • lab head:
    Paul Grimsrud
    • contact affiliation: Duke University
    • dataset submitter:

Full Dataset Link List

  1. jPOST dataset URI
  2. Dataset FTP location

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