PXD072219

PXD072219 is an original dataset announced via ProteomeXchange.

Title	Ebselen as a promising treatment in mitochondrial diseases: focus on Barth syndrome and complex I deficiencies
Description	Over the past decade, significant progress improved mitochondrial disorders diagnosis, but effective therapies remain lacking. A drug screening identified Ebselen (EBS) as enhancing oxidative phosphorylation-dependent growth in a yeast model of Barth syndrome, a cardiomyopathy caused by defective cardiolipin (CL) maturation, and in fungal models of other mitochondrial diseases involving defects in complex IV (CIV), mitochondrial DNA maintenance, mitochondrial translation, complex I (CI) and ATP synthase (CV), underlying Leigh syndrome, cytochrome c oxidase deficiency, hepatocerebral syndrome, MELAS, NARP and MILS. EBS also showed beneficial effects in human cells deficient in CL, CI, or CV, and in a CL-deficient mouse model. This organoselenium compound, known for its antioxidant and anti-inflammatory properties, is in phase III clinical trials for bipolar disorder and Meniere's disease. Our findings suggest that EBS’s rescuing activity is independent of inositol monophosphatase inhibition or antioxidant properties, which nonetheless support its potential use for these disorders. Our data reveal an undocumented mechanism of action that underlies the mitochondrial rescue induced by EBS. Its effect may involve (i) downregulation of cytosolic translation to restore proteostasis and (ii) pyruvate dehydrogenase complex-dependent stimulation of Krebs cycle to increase ATP yield, both potentially mTOR-dependent, as EBS accumulates in lysosomes. Thus, EBS holds promise as a therapeutic agent for Barth syndrome and a broader range of mitochondrial diseases.
HostingRepository	PRIDE
AnnounceDate	2026-09-03
AnnouncementXML	Submission_2026-09-03_07:10:24.822.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephane Claverol
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: NEWT:4932;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Eclipse; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-19 14:41:07	ID requested
⏵ 1	2026-09-03 07:10:25	announced

Dataset with its publication pending

submitter keyword: Barth syndrome

Mitochondrial diseases

drug repositioning

ebselen

Krebs cycle

cytosolic translation

Stephane Claverol
contact affiliation	Univ. Bordeaux, Bordeaux Proteome, Bordeaux, France
contact email	stephane.claverol@u-bordeaux.fr
lab head
Stephane Claverol
contact affiliation	Bordeaux Proteome
contact email	stephane.claverol@u-bordeaux.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072219
     1. Label: PRIDE project
     2. Name: Ebselen as a promising treatment in mitochondrial diseases: focus on Barth syndrome and complex I deficiencies