PXD035409-2

PXD035409 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial stress in GLA mutants Zebrafish is independent of globotriaosylceramide accumulation
Description	Fabry disease (FD) is a hereditary lysosomal storage disorder caused by mutations in GLA gene resulting in reduction or lack of α-galactosidase A activity. In humans, enzymatic deficiency leads to accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in lysosomes. Current therapies focus on reversing Gb3 accumulation but fail to restore altered cellular signaling in the long run. Zebrafish (ZF) lacks Alpha 1,4-Galactosyltransferase (A4GALT) gene and cannot synthesize Gb3 or lysoGb3. We used previously generated GLA-mutant ZF model to investigate Gb3-accumulation-independent alterations by untargeted proteomics analysis of renal tissues. We observed lysosomal and mitochondrial-related pathways disfunction, higher oxidative stress, as indicated by GSH/GSSH and MDA levels, and higher antioxidant activity in mutant ZF. Moreover, mitochondrial morphological alterations also affecting cristae structure were evident. By immunohistochemistry, we also detected decreased lysosomal Tetraspanin (CD63), Superoxide dismutase 2 (SOD2), and Cadherin 1 (CDH1) protein expression. Thus, this ZF model Gb3-independently mirrors GLA mutation-related changes, and unravels novel FD pathogenic mechanisms, thereby representing a powerful tool for innovative drug screening, and the identification of markers of potential clinical relevance.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:06:59.256.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Even Birkeland
SpeciesList	scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: 7955;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 00:55:51	ID requested
1	2023-10-24 11:02:01	announced
⏵ 2	2023-11-14 09:07:04	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:08:32	announced	2024-10-22: Updated project metadata.

Elsaid HOA, Rivedal M, Skandalou E, Svarstad E, T, ø, ndel C, Birkeland E, Eikrem Ø, Babickova J, Marti HP, Furriol J, zebrafish model of Fabry disease. J Transl Med, 21(1):591(2023) [pubmed]

submitter keyword: Alpha-galactosidase A/ Fabry disease/ lysosome/ mitochondrial activity/ proteomic approach

Jessica Furriol
contact affiliation	Department of Medicine, Haukeland University Hospital, Bergen, Norway
contact email	Jessica.furriol@gmail.com
lab head
Even Birkeland
contact affiliation	Institute of biomedicine, University of BErgen
contact email	even.birkeland@uib.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035409
     1. Label: PRIDE project
     2. Name: Mitochondrial stress in GLA mutants Zebrafish is independent of globotriaosylceramide accumulation