PXD049990

PXD049990 is an original dataset announced via ProteomeXchange.

Title	Multi-omics approach identifies a network of lipids and proteins associated to lysosomal and mitochondrial metabolism in Parkinson’s disease patients carrying mutations in TMEM175 gene.
Description	Parkinson’s disease (PD) represents one of the most frequent neurodegenerative disorders for which clinically useful biomarkers remain to be identified and validated for early and more precise diagnosis or for differentiation of disease subtypes, which may require different treatments. In this study we adopted an untargeted omics approach to disclose lipidomic, metabolomic and proteomic alterations in PD patients carrying TMEM175 mutations both in plasma and dermal fibroblasts. Integrated analysis of omics data revealed a wide dysregulation of lysosome, autophagy, and mitochondrial pathways in these PD patients, supporting a relevant role of this channel in regulating these cellular processes. The most significant altered lipid classes (CAR, Cer, FA, HexCer, PC, PC O-, SM, PI), and enzymes (PAG15, PP4P1, GALC, FYV1, PIGO, PGPS1, PLPP1) were involved in phosphosphingolipids and glycerophospholipids biosynthetic pathways. We also disclosed alterations of proteins involved in the insulin pathway (IGF2R), mitochondrial metabolism (ACD10, ACD11, ACADS) and autophagy (RAB7L). Interestingly, we also highlighted that the levels of CAR 18:2, HexCer 42:1;3O, and HexCer 42:2;3O, negatively correlated with age and age at onset (AAO) in PD patients. Strikingly, PI 34:1 was the only lipid showing a significant association with disease and a significant correlation (r=−0.5509; p=0.006) with age and earlier AAO of disease only in TMEM175 PD patients. All together these data provide novel insights into the molecular and metabolic alterations underlying TMEM175 mutations and may be relevant for PD prediction, diagnosis and treatment.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_13:15:50.209.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcello Manfredi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-21 06:53:04	ID requested
⏵ 1	2025-05-06 13:15:51	announced

10.1038/s41531-024-00853-5;

Carrillo F, Ghirimoldi M, Fortunato G, Palomba NP, Ianiro L, De Giorgis V, Khoso S, Giloni T, Pietracupa S, Modugno N, Barberis E, Manfredi M, Esposito T, Multiomics approach identifies dysregulated lipidomic and proteomic networks in Parkinson's disease patients mutated in TMEM175. NPJ Parkinsons Dis, 11(1):23(2025) [pubmed]

submitter keyword: Parkinson disease,Multi-omics, TMEM175 mutation

Marcello Manfredi
contact affiliation	Marcello Manfredi PhD Biological Mass Spectrometry Lab www.biomass-spec.com Department of Translational Medicine (DiMeT) https://www.agingproject.uniupo.it/ Center for Translational Research on Autoimmune & Allergic Diseases - CAAD University of Piemonte Orientale Corso Trieste 15/A, 28100, Novara, Italy Tel. 3334722270
contact email	marcello.manfredi@uniupo.it
lab head
Marcello Manfredi
contact affiliation	University of Eastern Piedmont
contact email	marcello.manfredi@uniupo.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049990
     1. Label: PRIDE project
     2. Name: Multi-omics approach identifies a network of lipids and proteins associated to lysosomal and mitochondrial metabolism in Parkinson’s disease patients carrying mutations in TMEM175 gene.