PXD059584

PXD059584 is an original dataset announced via ProteomeXchange.

Title	Novel in vivo models of autosomal optic atrophy show conserved pathological changes in mitochondrial structure and function ZEBRAFISH DATASET
Description	Autosomal optic atrophy (AOA) is a form of hereditary optic neuropathy characterized by the irreversible and progressive degermation of the retinal ganglion cells. Most cases of AOA are associated with a single dominant mutation in OPA1, which encodes a protein required for fusion of the inner mitochondrial membrane. It is unclear how loss of OPA1 leads to neuronal death, and despite ubiquitous expression appears to disproportionately affect the RGCs. This study introduces two novel in vivo models of OPA1-mediated AOA, including the first developmentally viable vertebrate Opa1 knockout (KO). These models allow for the study of Opa1 loss in neurons, specifically RGCs. Though survival is significantly reduced in Opa1 deficient zebrafish and Drosophila, both models permit the study of viable larvae. Moreover, zebrafish Opa1 KO larvae show impaired visual function but unchanged locomotor function, indicating that retinal neurons are particularly sensitive to Opa1 loss. Proteomic profiling of both models reveals marked disruption in protein expression associated with mitochondrial function, consistent with an observed decrease in mitochondrial respiratory function. Similarly, mitochondrial fragmentation and disordered cristae organization were observed in neuronal axons in both models highlighting Opa1’s highly conserved role in regulating mitochondrial morphology and function in neuronal axons. Importantly, in Opa1 deficient zebrafish, mitochondrial disruption and visual impairment precede degeneration of RGCs. These novel models mimic key features of AOA and provide valuable tools for therapeutic screening. Our findings suggest that therapies enhancing mitochondrial function may offer a potential treatment strategy for AOA.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_06:29:11.789.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD059584
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eugene Dillon
SpeciesList	scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: 7955;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-09 05:48:20	ID requested
⏵ 1	2025-05-07 06:29:12	announced

10.6019/PXD059584;

10.1096/fj.202403271r;

Strachan EL, Dillon ET, Sullivan M, Glennon JC, Peyrel A, Sarniguet J, Dubois K, Delprat B, Kennedy BN, O'Sullivan NC, vivo models of autosomal optic atrophy reveal conserved pathological changes in neuronal mitochondrial structure and function. FASEB J, 39(7):e70497(2025) [pubmed]

submitter keyword: Zebrafish

Drosophila

Mitochondria

Optic Atrophy

Visual Impairment. Project description:

Niamh O'Sullivan
contact affiliation	Lecturer/Associate Professor, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
contact email	niamh.osullivan@ucd.ie
lab head
Eugene Dillon
contact affiliation	UCD
contact email	eugene.dillon@ucd.ie
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/PXD059584

PRIDE project URI

• PRIDE
  1. PXD059584
     1. Label: PRIDE project
     2. Name: Novel in vivo models of autosomal optic atrophy show conserved pathological changes in mitochondrial structure and function ZEBRAFISH DATASET