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. 2021 Apr 26;3(5):636–650. doi: 10.1038/s42255-021-00385-9

Fig. 8. mtDNA-dependent innate immunity is coupled to cellular nucleotide metabolism.

Fig. 8

The i-AAA protease YME1L is required for efficient de novo pyrimidine synthesis and limits accumulation of the mitochondrial pyrimidine transporter SLC25A33. Loss of YME1L or cytosolic pyrimidine synthesis inhibition leads to an imbalance in cellular nucleotide pools. Deregulated mitochondrial nucleotide uptake and mtDNA replication may trigger the release of mtDNA into the cytosol. Cytosolic mtDNA is either degraded by the exonuclease TREX1 to replenish cytosolic nucleotide pools or binds to cGAS, which induces a STING-dependent innate immune response and autophagy.