PXD063591

PXD063591 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial dysfunction in Machado Joseph Disease: insights from a multi-model system
Description	Spinocerebellar ataxia type-3 (SCA3), also known as Machado Joseph disease, MJD) is a fatal, neurodegenerative disease belonging to the polyglutamine repeat disease family, caused by inheritance of an abnormal form of the ATXN3 gene, carrying a longer than usual trinucleotide repeat sequence. Within this study we explored mitochondrial function in a range of different experimental models of MJD, including transgenic zebrafish, mice and neuronal cells, to gain an understanding of mitochondrial function in the disease, and possible mechanisms of any dysfunction. Firstly, we examined the transgenic CMVMJD135 mouse model that develops impaired movement, neurodegeneration and decreased survival. We performed proteomic analysis on brain lysates extracted from a cohort of male and female WT and MJD mice, for analysis of differences in male and female mice separately. We identified that a major difference predicted by Ingenuity Pathway Analysis to be in both male and female MJD mice was related to impaired oxidative phosphorylation and mitochondrial dysfunction. We examined primary neuron cultures obtained from CMVMJD135 mice, validating the findings of the proteomic analysis, and finding changes to mitochondrial morphology, as well. We further examined a transgenic zebrafish model of MJD that expresses EGFP fused human ataxin-3 with short or long polyQ stretches (23 or 84Q, respectively) in neurons (expression driven under the elav/HuC promoter). The MJD zebrafish also exhibit altered mitochondrial electron transport chain complex protein levels, together with enhanced sensitivity to rotenone administration, which may be a valuable readout for treatment investigation studies in the future. Together, this study confirms, and extends on, the growing body of evidence suggesting that mitochondrial dysfunction plays a role in MJD, warranting investigation for therapeutic intervention.
HostingRepository	PRIDE
AnnounceDate	2026-08-24
AnnouncementXML	Submission_2026-08-24_05:06:01.990.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD063591
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Albert Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-04 17:26:20	ID requested
⏵ 1	2026-08-24 05:06:02	announced

10.1242/DMM.052757;

10.6019/PXD063591;

submitter keyword: oxidative phosphorylation, atxn3, MJD, mitochondria,machado joseph disease, mouse, polyQ, neurodegeneration

Albert Lee
contact affiliation	Motor Neuron Disease Research Centre, Macquarie University, Macquarie Park NSW 2109 Australia
contact email	albert.lee@mq.edu.au
lab head
Albert Lee
contact affiliation	Macquarie University
contact email	albert.lee@mq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063591
     1. Label: PRIDE project
     2. Name: Mitochondrial dysfunction in Machado Joseph Disease: insights from a multi-model system