PXD005854

PXD005854 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2017-02-06 01:40:30	ID requested
⏵ 1	2017-07-11 04:12:34	announced

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Translation, Mitochondria, oxidative phosphorylation, SILAC,Proteomics

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

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PRIDE project URI

• PRIDE
  1. PXD005854
     1. Label: PRIDE project
     2. Name: eIF2B links translational control to mitochondrial oxidative phosphorylation in Vanishing White Matter disease