PXD080411-1

PXD080411 is an original dataset announced via ProteomeXchange.

Title	Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response and promote progressive heart failure
Description	Mitochondrial DNA (mtDNA) mutations accumulate with age, but their mechanistic contribution to ageing remains unclear. The classical mtDNA mutator mouse expresses a proofreading-deficient mtDNA polymerase (POLGD257A) and accumulates mtDNA mutations across all tissues leading to premature ageing. However, this model cannot resolve whether the ageing phenotype results from systemic dysfunction or cell-intrinsic effects of somatic mtDNA mutations. To overcome this limitation, we generated PolgiMut mice allowing spatial and temporal control of POLGD257A expression. We demonstrate here that mtDNA mutations induced in cardiomyocytes cause progressive contractile dysfunction and respiratory chain deficiency in the heart without accompanying systemic pathology. Proteomic analyses link cardiac mosaic OXPHOS dysfunction to a progressive immune response, characterized by upregulation of antigen-processing proteins and immune cell infiltration. In contrast, longevity-associated pathways are suppressed and uncoupled from mitochondrial and immune alterations, indicating distinct regulatory mechanisms. These findings demonstrate that mtDNA mutations can drive cardiac dysfunction and reveal a mechanistic link between mitochondrial dysfunction, immune responses and ageing.
HostingRepository	PRIDE
AnnounceDate	2026-07-28
AnnouncementXML	Submission_2026-07-27_22:26:13.037.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-01 02:01:21	ID requested
⏵ 1	2026-07-27 22:26:13	announced

Dataset with its publication pending

submitter keyword: mtDNA, heart,Mouse, liver, mitochondria, spleen

Florian Rosenberger
contact affiliation	Max Planck Institute of Biochemistry, Dept. Proteomics and Signal Transduction, Martinsried, Germany
contact email	rosenberger@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD080411
     1. Label: PRIDE project
     2. Name: Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response and promote progressive heart failure