PXD053022

PXD053022 is an original dataset announced via ProteomeXchange.

Title	Dysregulated Skeletal Muscle Myosin Super-relaxation in Type II, but Not Type I, Diabetes Mellitus
Description	Skeletal muscle plays a critical role in the onset and development of type II diabetes. However, very few studies have investigated the potential pathogenic role of its most abundant protein, myosin. Hence, here, we aim to define this by focusing on myosin energy-saving state known as super-relaxed state (SRX). We performed an array of (loaded Mant-ATP chase experiments, LC-MS/MS proteomics, X-ray diffraction) assays on vastus lateralis biopsies from diabetic patients and matched controls. Strikingly, our results highlight that the amount of muscle myosin molecules in SRX is higher and the related ATP demand lower in type II diabetes patients than in controls. These physiological changes are parallel with greater glycation levels on myosin heavy chains, and with remodeled sarcomeric proteins in the same type II diabetes patients. None of these (mal)adaptations were noticed in patients with type I diabetes. Altogether, our findings emphasize a complex molecular dysregulation of myosin SRX and ATP consumption in type II diabetes. Ultimately, pharmacological targeting of SRX could benefit whole-body metabolic health through the enhancement of energy expenditure.
HostingRepository	PRIDE
AnnounceDate	2025-04-29
AnnouncementXML	Submission_2025-04-29_10:12:20.390.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roger Moreno Justicia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-11 11:55:23	ID requested
⏵ 1	2025-04-29 10:12:21	announced

10.1007/s00125-025-06436-0;

Lewis CTA, Moreno-Justicia R, Savoure L, Calvo E, Bak A, Laitila J, Seaborne RAE, Larsen S, Iwamoto H, Cefis M, Morais JA, Gouspillou G, Alegre-Cebollada J, Hawke TJ, Vazquez J, Adrover M, Marcangeli V, Hammad R, Granet J, Gaudreau P, Aubertin-Leheudre M, B, é, langer M, Robitaille R, Deshmukh AS, Ochala J, Dysregulated skeletal muscle myosin super-relaxation and energetics in male participants with type 2 diabetes mellitus. Diabetologia, ():(2025) [pubmed]

submitter keyword: proteomics, single muscle fiber, Skeletal muscle,Diabetes

Atul Shahaji Deshmukh
contact affiliation	University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research
contact email	atul.deshmukh@sund.ku.dk
lab head
Roger Moreno Justicia
contact affiliation	Novo Nordisk Foundation Center for Basic Metabolic Research
contact email	roger.moreno.justicia@sund.ku.dk
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/2025/04/PXD053022

PRIDE project URI

• PRIDE
  1. PXD053022
     1. Label: PRIDE project
     2. Name: Dysregulated Skeletal Muscle Myosin Super-relaxation in Type II, but Not Type I, Diabetes Mellitus