PXD005854 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | eIF2B links translational control to mitochondrial oxidative phosphorylation in Vanishing White Matter disease |
Description | Eukaryotic translation initiation factor 2B is a master regulator of protein synthesis under normal and stress conditions. Mutations in any of the five genes encoding its subunits lead to Vanishing White Matter (VWM) disease, a recessive genetic deadly illness caused by progressive loss of white matter in the brain. Although fibroblasts are not involved in the disease, we used mouse embryo fibroblasts (MEFs) isolated from Eif2b5R132H/R132H mice to demonstrate their compromised mitochondrial translation, unbalanced stoichiometry of proteins involved in oxidative phosphorylation, decreased basal and maximal oxygen consumption rate, and increased mitochondrial abundance reflecting adaptation to meet energy requirements. The involvement of eIF2B in mitochondrial function and abundance was validated in primary astrocytes isolated from Eif2b5R132H/R132H mice brains. We found that oxidative respiration deficiency is more robust in astrocytes and does not reach normal cellular levels even following 2-fols increase in mitochondrial content. The consequent increase in basal and maximal glycolysis in mutant astrocytes demonstrates their enhanced sensitivity to the impaired oxidative phosphorylation, illuminating the importance of mitochondrial function in VWM pathology. The data demonstrates the critical role of eIF2B in tight coordination of expression from nuclear and mitochondrial genomes. Further dissection of the signalling network associated with eIF2B function will help generating therapeutic strategies for VWM disease and possibly other neurodegenerative disorders. |
HostingRepository | PRIDE |
AnnounceDate | 2017-07-11 |
AnnouncementXML | Submission_2017-07-11_04:12:34.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Tamar Geiger |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-02-06 01:40:30 | ID requested | |
⏵ 1 | 2017-07-11 04:12:34 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
curator keyword: Biomedical |
submitter keyword: Translation, Mitochondria, oxidative phosphorylation, SILAC,Proteomics |
Contact List
Tamar Geiger |
contact affiliation | Department of Human Molecular Genetics and Biochemistry, Sackler faculty of Medecine, Tel Aviv University, Israel |
contact email | geiger@tauex.tau.ac.il |
lab head | |
Tamar Geiger |
contact affiliation | Tel Aviv University |
contact email | geiger@tauex.tau.ac.il |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD005854
- Label: PRIDE project
- Name: eIF2B links translational control to mitochondrial oxidative phosphorylation in Vanishing White Matter disease