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PXD019849-2

PXD019849 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNerv. System Specific Yme1l KO (NYKO) Mice Retina Samples (30-31wks old)
DescriptionCytosolic mitochondrial DNA (mtDNA) elicits a type I interferon response, but signals triggering the release of mtDNA from mitochondria remain enigmatic. We found that mtDNA-dependent immune signalling via the cGAS-STING pathway is under metabolic control and induced by cellular nucleotide deficiency. The mitochondrial protease YME1L preserves nucleotide pools by supporting de novo nucleotide synthesis and by proteolysis of the pyrimidine nucleotide carrier SLC25A33, limiting mitochondrial nucleotide transport and accumulation of mtDNA. Deficiency of YME1L or of the mitochondrial transcription factor A (TFAM) drives an mtDNA-dependent inflammatory response, which depends on SLC25A33 and is suppressed upon replenishment of cellular nucleotide pools. Depletion of cytosolic nucleotides upon starvation or downregulation of de novo nucleotide synthesis triggers mtDNA-dependent immune responses. Our results thus identify mtDNA release and innate immune signalling as a metabolic response, offering new therapeutic opportunities in disease.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:21:28.489.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHendrik Nolte
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-06-17 15:42:07ID requested
12021-04-28 01:18:20announced
22024-10-22 05:21:28announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Retina,NYKO
Contact List
Thomas Langer
contact affiliationMax-Planck-Institute for Biology of Ageing Department of Mitochondrial Proteostasis Joseph-Stelzmann-Str. 9b 50931 Cologne
contact emailtlanger@age.mpg.de
lab head
Hendrik Nolte
contact affiliationMax Planck Institute for Biology of Ageing, 50931 Cologne, Germany
contact emailh.nolte@age.mpg.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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