PXD013935

PXD013935 is an original dataset announced via ProteomeXchange.

Title	Disruption of acetyl group balance in cardiomyocytes augments the mitochondrial acetylproteome without affecting respiratory function or heart susceptibility to pressure overload
Description	Circumstantial evidence links the development of heart failure to perturbations in oxidative metabolism and corresponding shifts in post-translational modifications (PTMs) of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that acetyl-PTMs compromise mitochondrial performance remains sparse. Here, we used a respiratory diagnostics platform and serial assessment of cardiac phenotype to evaluate functional consequences of mitochondrial hyperacetylation caused by cardiac deficiency of carnitine acetyltransferase (CrAT) and sirtuin 3 (Sirt3); enzymes that oppose Kac by buffering the acetyl CoA pool and catalyzing lysine deacetylation, respectively. Although the dual knockout (DKO) manipulation raised the cardiac acetyl-lysine landscape well beyond that observed in response to Sirt3 deficiency or pathophysiological heart remodeling, bioenergetics of DKO mitochondria were remarkably normal. Moreover, DKO hearts were not more vulnerable to pressure overload-induced dysfunction resulting from chronic transaortic constriction. The findings challenge the premise that hyperacetylation per se threatens metabolic resilience by causing broad-ranging damage to mitochondrial proteins. See Davidson et. al. 2019 for further experimental details, reagents, and references.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:13:09.260.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Davidson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-20 05:59:35	ID requested
1	2020-10-01 23:31:33	announced
⏵ 2	2024-10-22 05:13:10	announced	2024-10-22: Updated project metadata.

10.1161/circresaha.120.317293;

Davidson MT, Grimsrud PA, Lai L, Draper JA, Fisher-Wellman KH, Narowski TM, Abraham DM, Koves TR, Kelly DP, Muoio DM, Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure. Circ Res, 127(8):1094-1108(2020) [pubmed]

submitter keyword: LC-MSMS, Mitochondria,Mouse, Heart, Acetylation

Deb Muoio
contact affiliation	Professor of Medicine, Division of Endocrinology, and Director of Basic Research at the Duke Molecular Physiology Institute
contact email	muoio@duke.edu
lab head
Michael Davidson
contact affiliation	Duke Molecular Physiology Institute
contact email	davidson.michael@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/2020/10/PXD013935

PRIDE project URI

• PRIDE
  1. PXD013935
     1. Label: PRIDE project
     2. Name: Disruption of acetyl group balance in cardiomyocytes augments the mitochondrial acetylproteome without affecting respiratory function or heart susceptibility to pressure overload