PXD047814

PXD047814 is an original dataset announced via ProteomeXchange.

Title	Iron deficiency causes aspartate-sensitive metabolic dysregulation in CD8+ T-cells
Description	Iron is an irreplaceable co-factor for important enzyme systems, and iron deficiency is the most common micronutrient deficiency worldwide. How iron deprivation influences normal cellular function remains poorly characterised. Using activated CD8+ T-cells as a model for dividing cells we show iron restriction causes specific and broad-acting metabolic defects. Iron scarcity altered gene expression, stalled proliferation and disrupted mitochondrial redox control.  TCA cycle was partially redirected to a reductive trajectory, depleting malate, fumarate and α-ketoglutarate, while the repressive H3K27me3 histone mark was maintained. Surprisingly, aspartate, which is crucial for dividing cells, was increased in stalled iron deficient cells. However, aspartate was not utilised cytosolically, suggesting trapping in depolarised mitochondria. Exogenous aspartate markedly rescued proliferation and function of iron-deprived T-cells, increasing ATP and decreasing H3K27me3. Therefore, iron scarcity creates a metabolic bottleneck that impairs cell division and function, but which can be bypassed without iron by resupplying biochemical processes with aspartate.
HostingRepository	PRIDE
AnnounceDate	2025-03-24
AnnouncementXML	Submission_2025-03-24_05:51:54.953.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Howden
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-13 21:33:56	ID requested
⏵ 1	2025-03-24 05:51:55	announced

Dataset with its publication pending

submitter keyword: metabolism, epigenetics, alpha-ketoglutarate, CD8+ T-cell, TCA cycle, OXPHOS, mitochondria,Iron, aspartate

Hal Drakesmith
contact affiliation	MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
contact email	alexander.drakesmith@ndm.ox.ac.uk
lab head
Andrew Howden
contact affiliation	University of Dundee
contact email	a.howden@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047814
     1. Label: PRIDE project
     2. Name: Iron deficiency causes aspartate-sensitive metabolic dysregulation in CD8+ T-cells