PXD053639-1

PXD053639 is an original dataset announced via ProteomeXchange.

Title	Subcellular fraction kidney proteomics in MGME1 knockout mice
Description	Metabolic dysregulation can lead to inflammatory responses. Imbalanced nucleotide synthesis triggers the release of mitochondrial DNA (mtDNA) to the cytosol and an innate immune response by cGAS-STING signaling. However, how nucleotide deficiency drives mtDNA dependent inflammation has not been elucidated. Here, we show that nucleotide imbalance leads to an increased misincorporation of ribonucleotides into mtDNA during age-dependent renal inflammation in a mouse model lacking the mitochondrial exonuclease MGME1 and upon inhibition of pyrimidine synthesis in cells lacking the mitochondrial i-AAA protease YME1L. Similarly, reduced deoxyribonucleotide synthesis increases ribonucleotide content of mtDNA in cell cycle-arrested senescent cells. This leads to mtDNA release into the cytosol, cGAS-STING activation and the mtDNA-dependent senescence-associated secretory phenotype (SASP), which can be suppressed by exogenously added deoxyribonucleotides. Our results explain age- and mtDNA-dependent inflammatory responses by imbalanced nucleotide metabolism and highlight the sensitivity of mtDNA to aberrant ribonucleotide incorporation.
HostingRepository	PRIDE
AnnounceDate	2025-07-25
AnnouncementXML	Submission_2025-07-25_06:21:18.908.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hendrik Nolte
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-04 05:44:09	ID requested
⏵ 1	2025-07-25 06:21:19	announced

Dataset with its publication pending

submitter keyword: mgme1, mitochondria,Kidney

Thomas Langer
contact affiliation	Max-Planck-Institute for Biology of Ageing Department of Mitochondrial Proteostasis Joseph-Stelzmann-Str. 9b
contact email	tlanger@age.mpg.de
lab head
Hendrik Nolte
contact affiliation	Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany
contact email	h.nolte@age.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/07/PXD053639

PRIDE project URI

• PRIDE
  1. PXD053639
     1. Label: PRIDE project
     2. Name: Subcellular fraction kidney proteomics in MGME1 knockout mice