PXD079332

PXD079332 is an original dataset announced via ProteomeXchange.

Title	Early cardiomyopathy in prediabetic NDPK-B-deficient mice is linked to dysregulated O-GlcNAcylation of mitochondrial proteins
Description	Diabetic cardiomyopathy (DCM) is initiated independently of other cardiac risk factors and is characterized by an early, often clinically silent decline in myocardial function. Nucleoside-diphosphate-kinase B (NDPK-B) plays a critical role in ion channel regulation and signal transduction, and its genetic deletion in middle-aged mice induces a phenotype resembling diabetic cardiomyopathy. The present study investigated the contribution of protein O-GlcNAcylation, driven by the hexosamine biosynthesis pathway (HBP), to the initiation and progression of DCM. NDPK-B-deficient prediabetic mice and streptozotocin-induced diabetic mice were examined. In both models, left ventricles (LV) exhibited increased extracellular matrix deposition and a marked diastolic dysfunction. Concomitantly, activation of the HBP was observed in prediabetic and diabetic LVs. Proteomic profiling of O-GlcNAcylated proteins revealed substantial dysregulation of mitochondrial proteins under prediabetic conditions, particularly affecting components of respiratory complex I, along with metabolic fuel reprogramming and activation of immune and inflammatory pathways. Progression to overt DCM was associated with a shift toward lipid-driven metabolic remodeling and profound structural mitochondrial impairment. These findings identify aberrant mitochondrial O-GlcNAcylation as a key early event in the initial stages of cardiac damage and reveal a mechanism involved in prediabetic cardiomyopathy.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-08_04:41:08.912.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuxi Feng
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2026-06-05 20:34:59	ID requested
⏵ 1	2026-06-08 04:41:09	announced

Dataset with its publication pending

submitter keyword: prediabetes

diabetes

NDPK-B

HBP

diabetic cardiomyopathy

mitochondria

Yuxi Feng
contact affiliation	Experimental Pharmacology Mannheim (EPM), European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
contact email	yuxi.feng@medma.uni-heidelberg.de
lab head
Yuxi Feng
contact affiliation	Experimental Pharmacology Mannheim (EPM), European Center of Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
contact email	yuxi.feng@medma.uni-heidelberg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD079332
     1. Label: PRIDE project
     2. Name: Early cardiomyopathy in prediabetic NDPK-B-deficient mice is linked to dysregulated O-GlcNAcylation of mitochondrial proteins