PXD028168

PXD028168 is an original dataset announced via ProteomeXchange.

Title	Intracellular lipid accumulation and mitochondrial dysfunction accompanies ER-stress caused by loss of the co-chaperone DNAJC3
Description	Recessive mutations in DNAJC3, an endoplasmic reticulum (ER)-resident BiP co-chaperone, have been identified in patients with multisystemic neurodegeneration and diabetes mellitus. To further unravel these pathomechanisms we employed a non-biased proteomic approach and identified dysregulation of several key cellular pathways, suggesting a pathophysiological interplay of perturbed lipid metabolism, mitochondrial bioenergetics, ER-Golgi function, and amyloid-beta processing. Further functional investigations in fibroblasts of patients with DNAJC3 mutations detected cellular accumulation of lipids, and an increased sensitivity to cholesterol-stress, which led to activation of the unfolded protein response (UPR), alterations of the ER-Golgi machinery, a defect of APP. In line with the results of previous studies, we describe here alterations in mitochondrial morphology and function, as a major contributor to the DNAJC3 pathophysiology. Hence, we propose that the loss of DNAJC3 affects lipid/cholesterol homeostasis, leading to UPR activation, Aβ accumulation and impairment of mitochondrial oxidative phosphorylation.
HostingRepository	PRIDE
AnnounceDate	2022-02-15
AnnouncementXML	Submission_2022-02-15_09:27:09.298.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Denisa Hathazi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-27 04:14:56	ID requested
⏵ 1	2022-02-15 09:27:10	announced

Jennings MJ, Hathazi D, Nguyen CDL, Munro B, M, ü, nchberg U, Ahrends R, Schenck A, Eidhof I, Freier E, Synofzik M, Horvath R, Roos A, . Front Cell Dev Biol, 9():710247(2021) [pubmed]

submitter keyword: Chaperonopathy, BiP, neuroproteomics, cholesterol-stress, β-amyloid

Dr. Andreas Roos
contact affiliation	1. Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany 2. Pediatric Neurology, University Hospital Essen, University of Duisburg-Essen, Faculty of Medicine, Essen, Germany
contact email	Andreas.Roos@uk-essen.de
lab head
Denisa Hathazi
contact affiliation	University of Cambridge, Department of Clinical Neurosciences, School of Clinical Medicine
contact email	gdh29@cam.ac.uk
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/2022/02/PXD028168

PRIDE project URI

• PRIDE
  1. PXD028168
     1. Label: PRIDE project
     2. Name: Intracellular lipid accumulation and mitochondrial dysfunction accompanies ER-stress caused by loss of the co-chaperone DNAJC3