PXD026495

PXD026495 is an original dataset announced via ProteomeXchange.

Title	THE INTRA-MITOCHONDRIAL O-GLCNACYLATION SYSTEM ACUTELY REGULATES OXPHOS CAPACITY AND ROS DYNAMICS IN THE HEART
Description	O-linked N-acetylglucosamination (O-GlcNAcylation) of proteins is increasingly recognized as an important cellular regulatory mechanism. In the heart, nucleocytoplasmic O-GlcNAcylation is involved in the modulation of multiple pathophysiological processes. However, the mechanisms leading to O-GlcNAcylation in mitochondria and the consequences on their function remain poorly understood. In this study, we used an in vitro reconstitution assay to characterize the intra-mitochondrial O-GlcNAc cycling system without potential confounding effects of O-GlcNAcylation in other cellular compartments. We performed a comparative analysis of the O-GlcNAcylome of isolated cardiac mitochondria acutely (30 min) exposed to UDP-GlcNAc in presence/absence of NButGT, a specific O-GlcNAcylation inducer, and evaluated the impact on mitochondrial function. 412 O-GlcNAcylated mitochondrial proteins were identified by mass spectrometry analysis, with 189 (Q<0.05) displaying increased O-GlcNAcylation in response to NButGT. Among the O-GlcNAcylated pathways identified, oxidative phosphorylation was the main affected. These acute changes in protein O-GlcNAcylation were associated with enhanced Complex I (CI) activity, increased maximal respiration in presence of CI substrates, and a striking reduction of mitochondrial ROS release, which could be related to O-GlcNAcylation of subunits within the NADH dehydrogenase module of CI. In conclusion, our work underlines the existence of a dynamic mitochondrial O-GlcNAcylation system capable of rapidly modifying mitochondrial function.
HostingRepository	PRIDE
AnnounceDate	2022-02-11
AnnouncementXML	Submission_2022-02-11_03:30:54.291.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD026495
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Didier Vertommen
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-04 09:37:36	ID requested
⏵ 1	2022-02-11 03:30:54	announced

Dataset with its publication pending

submitter keyword: heart, O-GlcNAc, mitochondria, oxidative phosphorylation

Luc Bertrand
contact affiliation	Pole of cardiovascular research - Institute of Experimental and Clinical Research (IREC) Université catholique de Louvain Brussels, Belgium
contact email	luc.bertrand@uclouvain.be
lab head
Didier Vertommen
contact affiliation	UCL - de Duve Institute, Brussels Belgium
contact email	didier.vertommen@uclouvain.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026495
     1. Label: PRIDE project
     2. Name: THE INTRA-MITOCHONDRIAL O-GLCNACYLATION SYSTEM ACUTELY REGULATES OXPHOS CAPACITY AND ROS DYNAMICS IN THE HEART