FIGURE 1.

Folate-mediated one-carbon metabolism. Cellular compartmentalization of FOCM. dTMP synthesis occurs in the cytosol, nucleus, and mitochondria, whereas purine synthesis and methionine synthesis take place within the cytosol. Mitochondrial FOCM generates formate for cytosolic and nuclear FOCM and biosynthetic precursors for mtDNA synthesis and mitochondrial protein translation. AICAR_Tfase, aminoimidazolecarboxamide ribonucleotide transformylase; ALDH1L2, aldehyde dehydrogenase 1 family member L2; DHF, dihydrofolate; DHFR, dihydrofolate reductase; dT, deoxythymidine; dTMP, deoxythymidine monophosphate; dUMP, deoxyuridine monophosphate; fMet, N-formylmethionine; FOCM, folate-mediated one-carbon metabolism; GAR_Tfase, glycinamide ribonucleotide tranformylase; GCS, glycine cleavage system; GTPBP3, GTP-binding protein 3, mitochondrial; mtDNA, mitochondrial DNA; MTFMT, mitochondrial methionyl-tRNA formyltransferase; MTHFD, methylenetetrahydrofolate dehydrogenase; MTHFD1L, methylenetetrahydrofolate dehydrogenase 1–like; MTHFR, methylene-tetrahydrofolate reductase; MTO1, mitochondrial tRNA translation optimization 1; MTR, methionine synthase; Pi, phosphate; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; SHMT, serine hydroxymethyltransferase; SUMO, small ubiquitin-like modifier; T, thymidine; THF, tetrahydrofolate; TK, thymidine kinase; TYMS, thymidylate synthase; U, uracil; τm⁵U, modified nucleoside 5-taurinomethyluridine.