PXD023881

PXD023881 is an original dataset announced via ProteomeXchange.

Title	Pyruvate kinase supports the metabolic shift and long-term survival of a mouse model with mitochondrial dysfunction caused by DGUOK deficiency
Description	The deoxyguanosine kinase (DGUOK) deficiency causes mtDNA depletion and mitochondrial dysfunction. We reported prolonged survival of Dguok knockout (Dguok-/-) mice despite low (<5%) mtDNA content in the liver. However, the molecular mechanisms, enabling the extended survival, remain unknown. Using transcriptomics, proteomics and metabolomics followed by in vitro assays, we aimed to identify the molecular pathways involved in the extended survival of Dguok-/- mice. At the early stage, the serine synthesis and folate cycle were activated but declined later. Increased activity of the mitochondrial citric acid cycle (TCA cycle) and the urea cycle and degradation of branched amino acids were hallmarks of the extended lifespan in DGUOK-deficiency. Furthermore, the increased synthesis of TCA cycle intermediates was supported by coordination of two pyruvate kinase genes, Pklr and Pkm, indicating a central coordinating role of pyruvate kinases to support the long-term survival in mitochondrial dysfunction.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_14:05:35.002.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akos Vegvari
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ FT

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-29 01:29:53	ID requested
⏵ 1	2022-02-16 14:05:36	announced

Zhou X, Mikaeloff F, Curbo S, Zhao Q, Kuiper R, V, é, gv, á, ri Á, Neogi U, Karlsson A, Coordinated pyruvate kinase activity is crucial for metabolic adaptation and cell survival during mitochondrial dysfunction. Hum Mol Genet, 30(21):2012-2026(2021) [pubmed]

submitter keyword: Mouse, Label-free quantification, TMT-based quantification, DGUOK deficiency

Akos Vegvari
contact affiliation	Division of Chemistry I, Department of Medical Biochemistry & Biphysics, Karolinska Institutet, Stockholm, Sweden
contact email	akos.vegvari@ki.se
lab head
Akos Vegvari
contact affiliation	Karolinska Institutet
contact email	akos.vegvari@ki.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023881
     1. Label: PRIDE project
     2. Name: Pyruvate kinase supports the metabolic shift and long-term survival of a mouse model with mitochondrial dysfunction caused by DGUOK deficiency