Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
  Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity

Sprenger, H.-G., MacVicar, T., Bahat, A., Fiedler, K. U., Hermans, S., Ehrentraut, D., et al. (2021). Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity. Nature Metabolism, 3(5), 636-650. doi:10.1038/s42255-021-00385-9.

Item is

Basisdaten

einblenden: ausblenden:
Genre: Zeitschriftenartikel

Externe Referenzen

einblenden:
ausblenden:
externe Referenz:
https://doi.org/10.1038/s42255-021-00385-9 (beliebiger Volltext)
Beschreibung:
-
OA-Status:
Keine Angabe

Urheber

einblenden:
ausblenden:
 Urheber:
Sprenger, H.-G.1, Autor           
MacVicar, T.1, Autor           
Bahat, A.1, Autor           
Fiedler, K. U.1, Autor           
Hermans, S.1, Autor           
Ehrentraut, D.1, Autor           
Ried, K.1, Autor           
Milenkovic, D.2, Autor           
Bonekamp, N.2, Autor           
Larsson, N.G.2, Autor           
Nolte, H.1, Autor           
Giavalisco, P.3, Autor           
Langer, T.1, Autor           
Affiliations:
1Department Langer - Mitochondrial Proteostasis, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3393994              
2Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942286              
3Metabolomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394018              

Inhalt

einblenden:
ausblenden:
Schlagwörter: -
 Zusammenfassung: Cytosolic mitochondrial DNA (mtDNA) elicits a type I interferon response, but signals triggering the release of mtDNA from mitochondria remain enigmatic. Here, we show that mtDNA-dependent immune signalling via the cyclic GMP–AMP synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS–STING–TBK1) pathway is under metabolic control and is induced by cellular pyrimidine deficiency. The mitochondrial protease YME1L preserves pyrimidine pools by supporting de novo nucleotide synthesis and by proteolysis of the pyrimidine nucleotide carrier SLC25A33. Deficiency of YME1L causes inflammation in mouse retinas and in cultured cells. It drives the release of mtDNA and a cGAS–STING–TBK1-dependent inflammatory response, which requires SLC25A33 and is suppressed upon replenishment of cellular pyrimidine pools. Overexpression of SLC25A33 is sufficient to induce immune signalling by mtDNA. Similarly, depletion of cytosolic nucleotides upon inhibition of de novo pyrimidine synthesis triggers mtDNA-dependent immune responses in wild-type cells. Our results thus identify mtDNA release and innate immune signalling as a metabolic response to cellular pyrimidine deficiencies.

Details

einblenden:
ausblenden:
Sprache(n):
 Datum: 2021-04-262021
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: DOI: 10.1038/s42255-021-00385-9
ISSN: 2522-5812
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: Nature Metabolism
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 3 (5) Artikelnummer: - Start- / Endseite: 636 - 650 Identifikator: -