PXD058697

PXD058697 is an original dataset announced via ProteomeXchange.

Title	Combined loss of obscurin and obscurin-like 1 in murine hearts results in diastolic dysfunction, altered metabolism and deregulated mitophagy.
Description	Background: Muscle proteins of the obscurin protein family play important roles in sarcomere organization, sarcoplasmic reticulum (SR) and T-tubule architecture and function. However, their precise molecular functions and redundancies between protein family members as well as their involvement in cardiac diseases remain to be fully understood. Methods: To investigate the functional roles of obscurin and its close homologue obscurin-like 1 (Obsl1) in the heart, we generated and analyzed knockout mice for obscurin, Obsl1, as well as obscurin/Obsl1 double-knockouts (dKO). Results: We show that dKO mice are viable but show postnatal deficits in cardiac muscle SR and mitochondrial architecture and function at the microscopic, biochemical, and cellular level. Altered SR structure resulted in perturbed calcium cycling, while mitochondrial ultrastructure deficits were linked to decreased levels of Chchd3, a Micos complex protein. Hearts of dKO mice also show altered levels of Atg4 proteins, novel Obsl1 interactors, resulting in abnormal mitophagy, and increased unfolded protein response. At the physiological level, loss of obscurin and Obsl1 resulted in a profound delay of cardiac relaxation, associated with metabolic signs of heart failure.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_05:30:15.926.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Majid Ghassemian
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iTRAQ8plex-116 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-09 09:54:51	ID requested
⏵ 1	2025-05-07 05:30:16	announced

Fujita K, Desmond P, Blondelle J, Sot, á, k M, Rajan MR, Clark M, Est, è, ve É, Chan Y, Gu Y, Actis Dato V, Marrocco V, Dalton ND, Ghassemian M, Do A, Klos M, Peterson KL, Sheikh F, Cho Y, B, ö, rgeson E, Lange S, Combined Loss of Obsc and Obsl1 in Murine Hearts Results in Diastolic Dysfunction, Altered Metabolism, and Deregulated Mitophagy. Circ Heart Fail, 18(4):e011867(2025) [pubmed]

10.1161/circheartfailure.124.011867;

ProteomeXchange project tag: Cardiovascular (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: mouse heart muscle iTRAQ obscurin

Stephan Lange
contact affiliation	Department of Biomedicine, Aarhus University, Aarhus, Denmark STENO Diabetes Center Aarhus, Aarhus, Denmark
contact email	stephan.lange@biomed.au.dk
lab head
Majid Ghassemian
contact affiliation	Scientist
contact email	mghassem@ucsd.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/2025/05/PXD058697

PRIDE project URI

• PRIDE
  1. PXD058697
     1. Label: PRIDE project
     2. Name: Combined loss of obscurin and obscurin-like 1 in murine hearts results in diastolic dysfunction, altered metabolism and deregulated mitophagy.