PXD007881

PXD007881 is an original dataset announced via ProteomeXchange.

Title	Disease-linked lysine glutarylation impairs function and interactions of mitochondrial proteins and contribute to mitochondrial heterogeneity
Description	Inherited deficiencies of the lysine and tryptophan catabolic pathways, due to mutations in the glutaryl-CoA-dehydrogenase (GCDH) gene, cause glutaric aciduria type 1 (GA1). In mammals two metabolic routes for L-lysine oxidation exist, the mitochondrial saccharopine pathway, which is predominant in extracerebral tissue and the peroxysomal/cytosolic pipecolate pathway, the main pathway in adult brain. A unique feature of all pathways is the formation of glutaryl-CoA that is converted into crotonyl-CoA via GCDH. In this study we identified increased lysine glutarylation, a novel reversible post-translational modification, in various tissues and cultured cells of Gcdh KO mice as a result of glutaryl-CoA accumulation. Our analysis revealed that glutarylation is widespread in mitochondria. By using a proteomic approach, we identified 37 and 154 glutarylated mitochondrial proteins in brain and liver tissue from Gcdh KO mice, respectively. We further showed that glutarylation supresses glutamate dehydrogenase (GDH) and carbonic anhydrase 5B activity, plus the direct interaction between GCDH and GDH.
HostingRepository	PRIDE
AnnounceDate	2018-07-11
AnnouncementXML	Submission_2018-09-17_00:13:30.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marc Sylvester
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-02 01:36:41	ID requested
1	2018-07-11 03:51:33	announced
2	2018-07-11 08:52:36	announced	Updated project metadata.
⏵ 3	2018-09-17 00:13:31	announced	Updated project metadata.

Schmiesing J, Storch S, D, ö, rfler AC, Schweizer M, Makrypidi-Fraune G, Thelen M, Sylvester M, Gieselmann V, Meyer-Schwesinger C, Koch-Nolte F, Tidow H, M, ü, hlhausen C, Waheed A, Sly WS, Braulke T, Disease-Linked Glutarylation Impairs Function and Interactions of Mitochondrial Proteins and Contributes to Mitochondrial Heterogeneity. Cell Rep, 24(11):2946-2956(2018) [pubmed]

curator keyword: Biological

submitter keyword: glutaryl-CoA-dehydrogenase, glutaryl-proteome, glutamate dehydrogenase, protein interaction, Post-translational Modifications, Proteolysis & Proteomics, Metabolism, Molecular Biology of Disease

Thomas Braulke
contact affiliation	University Medical Center Hamburg-Eppendorf, Children´s Hospital Department of Biochemistry Hamburg, Germany
contact email	braulke@uke.de
lab head
Marc Sylvester
contact affiliation	University of Bonn, Institute of Biochemistry and Molecular Biology
contact email	msylvest@uni-bonn.de
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/2018/07/PXD007881

PRIDE project URI

• PRIDE
  1. PXD007881
     1. Label: PRIDE project
     2. Name: Disease-linked lysine glutarylation impairs function and interactions of mitochondrial proteins and contribute to mitochondrial heterogeneity