PXD011375

PXD011375 is an original dataset announced via ProteomeXchange.

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.
HostingRepository	jPOST
AnnounceDate	2019-02-07
AnnouncementXML	Submission_2022-09-18_02:23:13.497.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Grimsrud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; TMT6plex reporter+balance reagent N-acylated residue; N6-malonyl-L-lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-16 06:45:57	ID requested
1	2019-02-07 05:59:53	announced
2	2021-02-04 17:35:09	announced	2021-02-04: Updated FTP location.
⏵ 3	2022-09-18 02:23:14	announced	2022-09-18: Updated FTP location.

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]

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

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

jPOST dataset URI

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