PXD003155

PXD003155 is an original dataset announced via ProteomeXchange.

Title	Atxn2-Knock-Out mice show branched chain amino acids and fatty acids pathway alterations
Description	Human Ataxin-2 (ATXN2) gene locus variants have been associated with obesity, diabetes mellitus type 1 and hypertension in genome-wide association studies, while mouse studies showed the knock-out of Atxn2 to lead to obesity, insulin resistance and dyslipidemia. Intriguingly, the deficiency of ATXN2 protein orthologues in yeast and flies rescues the neurodegeneration process triggered by TDP-43 and Ataxin-1 toxicity. To understand the molecular effects of ATXN2 deficiency by unbiased approaches, we quantified the global proteome and metabolome of Atxn2-knock-out mice with label-free mass spectrometry. In liver tissue, significant downregulations of the proteins ACADS, ALDH6A1, ALDH7A1, IVD, MCCC2, PCCA, OTC, together with bioinformatic enrichment of downregulated pathways for branched chain and other amino acid metabolism, fatty acids and citric acid cycle were observed. Statistical trends in the cerebellar proteome and in the metabolomic profiles supported these findings. They are in good agreement with recent claims that PBP1, the yeast orthologue of ATXN2, sequestrates the nutrient sensor TORC1 in periods of cell stress. Overall, ATXN2 appears to modulate nutrition and metabolism, and its activity changes are determinants of growth excess or cell atrophy.
HostingRepository	PRIDE
AnnounceDate	2016-02-08
AnnouncementXML	Submission_2016-02-08_01:38:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Meierhofer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-11-06 00:08:46	ID requested
⏵ 1	2016-02-08 01:38:03	announced

Meierhofer D, Halbach M, Ş, en NE, Gispert S, Auburger G, Ataxin-2 (Atxn2)-Knock-Out Mice Show Branched Chain Amino Acids and Fatty Acids Pathway Alterations. Mol Cell Proteomics, 15(5):1728-39(2016) [pubmed]

curator keyword: Biological

submitter keyword: Spinocerebellar Ataxia type 2 (Atxn2)

mass spectrometry

proteome profiling

metabolome profiling

multiple reaction monitoring (MRM)

protein - protein interaction network (PPI) analysis

pathway analysis.

David Meierhofer
contact affiliation	Mass Spectrometry Facility, Max Planck Institute for Molecular Genetics (MPIMG), Berlin, Germany
contact email	Meierhof@molgen.mpg.de
lab head
David Meierhofer
contact affiliation	Mass Spectrometry Facility MPIMG
contact email	meierhof@molgen.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003155
     1. Label: PRIDE project
     2. Name: Atxn2-Knock-Out mice show branched chain amino acids and fatty acids pathway alterations