GSE161734 Cellular nucleotide deficiency triggers mitochondrial DNA-dependent innate immunity [Scr_vs_Yme1l-si_RNA-seq]

Contributors : Hans-Georg Sprenger ; Thomas MacVicar ; Janine Altm üllerSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusCytosolic 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. 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.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research