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PXD027372 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLoss of DNAJC3 impairs cholesterol metabolism and mitochondrial function
DescriptionRecessive mutations in DNACJ3, an endoplasmic reticulum (ER)-resident BiP co-chaperone, have been identified in patients with multisystemic neurodegeneration and diabetes mellitus. While minor ER morphology changes due to loss of DNAJC3 have been reported previously, the precise cellular pathophysiology is still elusive and not well understood. To further elucidate the cellular consequences of DNAJC3 loss we employed a non-biased proteomic approach and identified dysregulation of several key cellular pathways implying a pathophysiological interplay of perturbed lipid metabolism, mitochondrial bioenergics, 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 UPR, alterations of the ER-Golgi machinery, a defect of APP processing and concomitant Aβ accumulation. Moreover, we described here for the first-time alterations in mitochondrial morphology and oxidative phosphorylation as a major contributor to the DNAJC3 pathophysiology. Hence, we propose that the loss of DNAJC3 affects the lipid/cholesterol homeostasis, leading to UPR activation, Aβ accumulation and impaired protection against mitochondrial oxidative stress.
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterChi Nguyen
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListCarbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-07-16 07:57:15ID requested
12021-07-17 07:49:23announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Targeted Proteomics, PRM
Contact List
Robert Ahrends
contact affiliationLeibniz-Institute for Analytical Science – ISAS – e.V.
contact emailrobert.ahrends@univie.ac.at
lab head
Chi Nguyen
contact affiliationLeibniz-Institut für Analytische Wissenschaften – ISAS – e.V.
contact emailchi.nguyen@isas.de
dataset submitter
Full Dataset Link List
Panorama Public dataset URI