PXD048682-1

PXD048682 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial calcium uniporter complex controls T‑cell‑mediated immune responses
Description	Sustained and balanced calcium (Ca2+) increase upon T-cell receptor activation is a fundamental process that regulates essential T-cell functions including proliferation, clonal expansion and cytokine secretion. In this context, mitochondria play an important role and take up Ca2+ to support the elevated bioenergetic demands. Accordingly, alterations in the protein machinery that regulates mitochondrial Ca2+ (mCa2+) flux across the inner mitochondrial membrane; the mitochondrial calcium uniporter (MCU) complex, could be implicated in T-cell immunity. However, the exact role of mCa2+, and thus MCU in T-cells is not fully understood. Here, we show that upon activation of primary human CD4+ T-cells, the MCU complex undergoes a time-dependent compositional rearrangement that causes elevated mCa2+ uptake and increased mitochondrial bioenergetic output. Transcriptome and proteome analyses of naive and effector CD4+ T-cells reveal molecular determinants involved in mitochondrial and T-cell functional reprograming. Moreover, they identify genes, proteins and signaling pathways controlled by mitochondrial Ca2+ homeostasis i.e. the MCU. MCUa knockdown (KD) diminishes mCa2+, mitochondrial respiration and ATP production as well as T-cell invasion and cytokine secretion. In vivo, downregulation of MCUa in rat CD4+ T-cells suppresses autoimmune responses in a multiple sclerosis model of inflammatory experimental autoimmune encephalomyelitis (EAE). In summary, our findings imply that mCa2+ uptake through MCU is essential for proper T-cell function and is involved in autoimmunity. Specific MCU inhibitors targeting T-cells could be beneficial for autoimmune suppression and control of immune system dysregulation.
HostingRepository	PRIDE
AnnounceDate	2024-10-24
AnnouncementXML	Submission_2024-10-24_06:05:26.709.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Prerana Wagle
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-18 06:40:25	ID requested
⏵ 1	2024-10-24 06:05:27	announced

Dataset with its publication pending

submitter keyword: MCU/autoimmunity/calcium/EAE/metabolism/mitochondria/T-cell

Jan Riemer
contact affiliation	Department of Redox Metabolism, Institute of Biochemistry, University of Cologne, Cologne, Germany
contact email	jan.riemer@uni-koeln.de
lab head
Prerana Wagle
contact affiliation	CECAD Research Center
contact email	proteomics-facility@uni-koeln.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048682
     1. Label: PRIDE project
     2. Name: Mitochondrial calcium uniporter complex controls T‑cell‑mediated immune responses