PXD014586

PXD014586 is an original dataset announced via ProteomeXchange.

Title	Disruption of acetyl-lysine turnover in muscle mitochondria promotes insulin resistance and redox stress without overt respiratory dysfunction
Description	A double knockout (DKO) mouse model harboring muscle-specific deficits in acetyl CoA buffering by carnitine acetyltransferase (CrAT), and lysine deacetylation by SIRT3, resulted in additive hyperacetylation of the mitochondrial proteome, which was augmented exponentially by chronic high fat feeding. Whereas DKO mice developed a more severe form of diet-induced insulin resistance than either single KO mouse line, the functional profiles of hyperacetylated mitochondria were largely negative. Of the >120 measures of respiratory kinetics and thermodynamics assayed in DKO skeletal muscle mitochondria, the most consistently observed traits of a markedly heightened acetyl-lysine landscape were enhanced oxygen flux in the context of a long chain fatty acid fuel, and elevated rates of complex I-dependent electron leak. In sum, the findings challenge the notion that lysine acetylation causes broad-ranging damage to mitochondrial quality and performance, and raise the possibility that acetyl-lysine turnover, rather than acetyl-lysine stoichiometry, modulates redox balance and carbon flux.
HostingRepository	PRIDE
AnnounceDate	2019-11-25
AnnouncementXML	Submission_2020-01-14_07:34:44.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	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-12 01:19:47	ID requested
1	2019-11-25 09:33:16	announced
⏵ 2	2020-01-14 07:34:46	announced	2020-01-14: Updated publication reference for PubMed record(s): 31813822.

Williams AS, Koves TR, Davidson MT, Crown SB, Fisher-Wellman KH, Torres MJ, Draper JA, Narowski TM, Slentz DH, Lantier L, Wasserman DH, Grimsrud PA, Muoio DM, Disruption of Acetyl-Lysine Turnover in Muscle Mitochondria Promotes Insulin Resistance and Redox Stress without Overt Respiratory Dysfunction. Cell Metab, 31(1):131-147.e11(2020) [pubmed]

submitter keyword: Mitochondrial Bioenergetics, Protein Acetylation, Insulin Resistance

Deborah M. Muoio
contact affiliation	Director of Basic Research, Duke Molecular Physiology Institute Professor, Department of Medicine, Duke University Medical Center
contact email	debbie.muoio@duke.edu
lab head
Paul Grimsrud
contact affiliation	Duke Molecular Physiology Institute
contact email	paul.grimsrud@duke.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/11/PXD014586

PRIDE project URI

• PRIDE
  1. PXD014586
     1. Label: PRIDE project
     2. Name: Disruption of acetyl-lysine turnover in muscle mitochondria promotes insulin resistance and redox stress without overt respiratory dysfunction