PXD016698

PXD016698 is an original dataset announced via ProteomeXchange.

Title	Metabolic changes related to the IDH1 mutation in gliomas preserve TCA-cycle activity: an investigation at the protein level
Description	The discovery of the IDH1 R132H (IDH1 mut) mutation in low-grade glioma and the associated change in function of the IDH1 enzyme has increased the interest in glioma metabolism. In an earlier study, we found that changes in expression of genes involved in the aerobic glycolysis and the TCA-cycle are associated with IDH1 mut. Here we apply proteomics to FFPE samples of diffuse gliomas with or without IDH1 mutations, in order to map changes in protein levels associated with this mutation. We observed significant changes in the enzyme abundance associated with aerobic glycolysis, glutamate metabolism and the TCA-cycle in IDH1 mut gliomas. Specifically, the enzymes involved in the metabolism of glutamate, lactate and enzymes involved in the conversion of α-ketoglutarate were increased in IDH1 mut gliomas. In addition, the bicarbonate transporter (SLC4A4) was increased in IDH1 mut gliomas, supporting the idea that a mechanism preventing intracellular acidification is active. We also found that enzymes that convert proline, valine, leucine and isoleucine into glutamate were increased in IDH1 mut glioma. We conclude that in IDH1 mut glioma metabolism is rewired (increased input of lactate and glutamate) to preserve TCA cycle activity in IDH1 mut gliomas.
HostingRepository	PRIDE
AnnounceDate	2020-03-09
AnnouncementXML	Submission_2020-03-09_06:47:08.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD016698
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Lennard Dekker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-11 04:10:26	ID requested
⏵ 1	2020-03-09 06:47:10	announced

Dekker LJM, Wu S, Jurri, ë, ns C, Mustafa DAN, Grevers F, Burgers PC, Sillevis Smitt PAE, Kros JM, Luider TM, Metabolic changes related to the IDH1 mutation in gliomas preserve TCA-cycle activity: An investigation at the protein level. FASEB J, 34(3):3646-3657(2020) [pubmed]

submitter keyword: Glioma, metabolism, proteomics, IDH1

Theo Luider
contact affiliation	ErasmusMC Neurology Laboratory of clinical and cancer proteomics Rotterdam The Netherlands
contact email	t.luider@erasmusmc.nl
lab head
Lennard Dekker
contact affiliation	Erasmus MC
contact email	l.dekker@erasmusmc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016698
     1. Label: PRIDE project
     2. Name: Metabolic changes related to the IDH1 mutation in gliomas preserve TCA-cycle activity: an investigation at the protein level