PXD069191

PXD069191 is an original dataset announced via ProteomeXchange.

Title	Integrated mitochondrial profiling identifies mitochondrial gene expression and membrane potential in IL-4/IL-13 macrophages
Description	Macrophage activation triggers intense genetic and immunometabolic reprograming that support distinct macrophage functions, and mitochondria are central to this process. To date, the extent to which they are remodeled and how this impacts macrophage function remains unclear. Here, we integrate transcriptomics with whole-cell and highly purified mitochondrial proteomics to profile LPS/IFNγ- andIL-4/IL-13-stimulated bone-marrow–derived macrophages (BMDM). We uncover a striking disconnect between mitochondrial transcripts and proteins and identify a STAT6-dependent increase in mitochondrial gene expression and intramitochondrial translation as hallmarks of IL-4/IL-13 stimulation. Pharmacological blockade of mitochondrial translation or individual respiratory chain complexes impairs activation, while ATP synthase inhibition uniquely triggers mitochondrial hyperpolarization and the integrated stress response, halting IL-4/IL-13 activation. Restoring mitochondrial membrane potential or inhibiting the stress response rescues effector synthesis. Together, we establish mitochondrial gene expression and membrane potential as regulators of macrophage immunometabolism and identify mitochondrial translation as a critical, drug-sensitive determinant of IL-4/IL-13 macrophage function.
HostingRepository	PRIDE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-29_15:57:48.327.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexis Jourdain
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-07 14:07:14	ID requested
⏵ 1	2026-06-29 15:57:48	announced

Dataset with its publication pending

submitter keyword: mtDNA, integrated stress response, proteomics, membrane potential, OXPHOS, immunometabolism, mitochondria,Macrophage, IL-4, IL-13

Alexis Jourdain
contact affiliation	Dpt. of Immunobiology, University of Lausanne (UNIL). Ch.Boveresses 155 CH-1066 Epalinges
contact email	alexis.jourdain@unil.ch
lab head
Alexis Jourdain
contact affiliation	Department of Immunobiology, University of Lausanne
contact email	alexis.jourdain@unil.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069191
     1. Label: PRIDE project
     2. Name: Integrated mitochondrial profiling identifies mitochondrial gene expression and membrane potential in IL-4/IL-13 macrophages