PXD048152

PXD048152 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	UBQLN2 Governs Lipid Metabolism Linked to Neurodegeneration in ALS/FTD
Description	Missense mutations in UBQLN2, a protein quality control factor, are associated with neurodegenerative diseases amyotrophic lateral sclerosis (ALS) overlapping with frontotemporal dementia (FTD). The mechanisms by which these mutations lead to neurodegeneration are not fully understood. Here we describe a critical role for UBQLN2 in regulating cellular lipid metabolism, which is crucial for cell survival under nutrient stress. The stress dependent regulation of lipid metabolism by UBQLN2 is mediated by ILVBL, a UBQLN2 substrate and a key enzyme in lipid turnover. The function of UBQLN2 in promoting ILVBL degradation and maintaining intracellular lipids was compromised by ALS/FTD-linked mutations in UBQLN2. As a result of the lipid dysregulation, synaptic vesicles were deficient and neuronal death was exacerbated in mutant UBQLN2 transgenic mice or human iPSCs derived motor neurons and cortical organoids. Replenishing lipids or restoring UBQLN2 function could reverse the deficits in the UBQLN2 mutant neurons under nutrient stress. Our study reveals UBQLN2 essential role in lipid metabolism and suggests metabolic imbalance underlying ALS/FTD and related neurodegenerative conditions.
HostingRepository	MassIVE
AnnounceDate	2023-12-27
AnnouncementXML	Submission_2023-12-27_18:42:33.633.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ling Hao
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Oxidation; Acetyl
Instrument	Q Exactive HF-X

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-27 18:21:04	ID requested
⏵ 1	2023-12-27 18:42:33	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: UBQLN2, ALS, FTD, frontotemporal dementia , amyotrophic lateral sclerosis , motor neuron, dynamic SILAC, dSILAC, SILAC, pSILAC

submitter keyword: UBQLN2, ALS, FTD, frontotemporal dementia , amyotrophic lateral sclerosis , motor neuron, dynamic SILAC, dSILAC, SILAC, pSILAC

Contact List

Ling Hao
contact affiliation	The George Washington University
contact email	linghao@gwu.edu
lab head
Ling Hao
contact affiliation	George Washington University
contact email	haolab.19@gmail.com
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

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://massive.ucsd.edu/MSV000093732/