Figure 7.

Proposed model. Three primary sources of the mitochondrial dTMP pool are shown. Red, source 1: salvage dTMP synthesis using dT from cytosolic and mitochondrial pools. Salvage synthesis of dTMP is independent of folate status; it relies on TK2 activity to convert dT to dTMP. Mitochondrial pyrimidine nucleotide transporter PNC1 facilitates the import of dT from cytosolic pools. Blue, source 2: de novo dTMP synthesis using dUMP from mitochondrial and cytosolic pools. Cytosolic dUMP is imported into the mitochondria via PNC2, where it participates in folate-dependent de novo dTMP biosynthesis. Purple, source 3: transport dTMP from cytosolic pools, to be incorporated into the mitochondrial dTMP pool. dTMP synthesized in the cytosol via the salvage pathway or de novo pathway is imported into the mitochondria to help sustain mtDNA synthesis; the mitochondrial import of synthesized dTMP is perturbed under MPV17-deficient conditions.