PXD056395-1

PXD056395 is an original dataset announced via ProteomeXchange.

Title	Multi-omics-based phenotyping of AFG3L2-mutant lymphoblasts determines key factors of a pathophysiological interplay between mitochondrial vulnerability and neurodegeneration in spastic ataxia type 5
Description	This study employs a multi-omics approach to investigate the biochemical impact of AFG3L2 mutations in immortalized lymphoblastoid cell lines derived from a SPAX5 patient. Our proteomic analysis revealed significant dysregulation in proteins involved in mitochondrial function, cytoskeletal integrity, and cellular metabolism. Specifically, we observed disruptions in mitochondrial dynamics and calcium homeostasis, characterized by the downregulation of critical mitochondrial proteins such as COX11 and NFU1, and upregulation of key regulatory proteins like PRKCB and KCTD12. Consistent with this, metabolomic profiling identified a marked reduction in acetyl-CoA levels, indicating impaired TCA cycle activity and potential energy deficits. Lipidomic analysis highlighted substantial alterations in lipid composition, with significant decreases in sphingomyelins, phosphatidylethanolamine, and phosphatidylcholine, reflecting disruptions in lipid metabolism and membrane integrity. Our comprehensive investigation into AFG3L2 deficiency elucidates a pathophysiology extending beyond mitochondrial proteostasis, implicating a wide array of cellular processes. The findings reveal substantial cellular disturbances at multiple levels, contributing to neurodegeneration through disrupted mitochondrial calcium homeostasis, cytoskeletal integrity, and altered metabolic and lipid homeostasis. This study underscores the complexity of SPAX5 pathophysiology and the importance of multi-omics approaches in developing effective strategies to address the impact of AFG3L2 deficiency. Our data also highlight the value of immortalized lymphoblastoid cells as a tool for pre-clinical testing and research, offering a detailed biochemical fingerprint that enhances our understanding of SPAX5 and identifies potential areas for further investigation.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_03:27:24.427.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Hentschel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-30 07:01:31	ID requested
⏵ 1	2025-05-07 03:27:25	announced

10.3389/fnmol.2025.1548255;

Oeztuerk M, Herebian D, Dipali K, Hentschel A, Rademacher N, Kraft F, Horvath R, Distelmaier F, Meuth SG, Ruck T, Schara-Schmidt U, Roos A, Multi-omics-based phenotyping of AFG3L2-mutant lymphoblasts determines key factors of a pathophysiological interplay between mitochondrial vulnerability and neurodegeneration in spastic ataxia type 5. Front Mol Neurosci, 18():1548255(2025) [pubmed]

submitter keyword: MCU, multi-omics lymphoblasts, SPAX5,AFG3 like matrix AAA peptidase subunit 2, liquid biopsy

Prof. Dr. Albert Sickmann
contact affiliation	Proteomics, Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany
contact email	Albert.Sickmann@isas.de
lab head
Andreas Hentschel
contact affiliation	Leibniz Institut für Analytische Wissenschaften
contact email	andreas.hentschel@isas.de
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/PXD056395

PRIDE project URI

• PRIDE
  1. PXD056395
     1. Label: PRIDE project
     2. Name: Multi-omics-based phenotyping of AFG3L2-mutant lymphoblasts determines key factors of a pathophysiological interplay between mitochondrial vulnerability and neurodegeneration in spastic ataxia type 5