PXD060450-1

PXD060450 is an original dataset announced via ProteomeXchange.

Title	Optic Atrophy 1 (OPA1) overexpression promotes dyslipidemia and atherosclerosis coupled to altered aortic VSMC function in LDL-R deficient mice
Description	OPA1 (Optic Atrophy 1), a mitochondrial inner membrane protein involved in mitochondrial cellular metabolism, energy production, calcium homeostasis, and sterol and bile acids (BAs) synthesis. Mitochondria are plastic organelles continuously undergoing biogenesis, fusion, fission, and mitophagy. On these premises, we tested how the overexpression of OPA1, an inner mitochondrial membrane fusion protein, impacts lipids, lipoprotein metabolism, and atherosclerosis development in LDL-R deficient mice (LDLR KO). Methods: OPA1TG/LDLR KO and OPA1ΔHep /LDLR KO were generated and fed with a Western-type diet (WTD) for 12 weeks. Atherosclerosis development was compared to that of LDLR KO mice. In humans, OPA1 expression was investigated in samples from 78 asymptomatic and symptomatic human subjects within the Carotid Plaque Imaging Project (CPIP). Results: OPA1TG/LDLR KO mice showed a significant increase in plasma cholesterol levels mainly in VLDL and LDL fractions. OPA1TG/LDLR KO display a reduction of unconjugated bile acids and higher percentage of conjugated bile acids leading to an increased lipid adsorption. This phenotype was associated with increased atherosclerosis in the aortic root. OPA1 overexpression affects also vascular smooth muscle cell cellular metabolism, leading to an increase in the synthetic vs the proliferative phenotype. Vice versa, hepatocyte deletion of OPA1 improved systemic lipoprotein metabolism and protected from atherosclerosis. The analysis of human atherosclerotic samples indicated that a higher OPA1 expression in the plaque is associated with a reduced degradation of extracellular matrix as well as the expression of markers of cell migration and differentiation. Conclusion: Mitochondrial fusion mediated by OPA1 plays a key role in atherosclerosis by affecting lipoprotein metabolism as well as vascular smooth muscle cell biology.
HostingRepository	PRIDE
AnnounceDate	2025-10-27
AnnouncementXML	Submission_2025-10-26_17:34:02.794.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Monika Svecla
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-04 01:53:49	ID requested
⏵ 1	2025-10-26 17:34:03	announced

10.1016/j.molmet.2025.102256;

Da Dalt L, Fantini F, Giancane G, Moregola A, Roda S, Svecla M, Pedretti S, Vingiani GB, Sun J, Edsfeldt A, Goncalves I, Uboldi P, Donetti E, Baragetti A, Mitro N, Scorrano L, Norata GD, Increased mitochondrial fusion via systemic OPA1 overexpression promotes dyslipidemia and atherosclerosis in LDLR deficient mice. Mol Metab, 102():102256(2025) [pubmed]

submitter keyword: Mouse, Proteomics

Giuseppe Danilo Norata
contact affiliation	Professor of Pharmacology, University of Milan, Italy
contact email	danilo.norata@unimi.it
lab head
Monika Svecla
contact affiliation	University of Milan
contact email	monika.svecla@unimi.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060450
     1. Label: PRIDE project
     2. Name: Optic Atrophy 1 (OPA1) overexpression promotes dyslipidemia and atherosclerosis coupled to altered aortic VSMC function in LDL-R deficient mice