Figure 5: Schematic representation of plant SAM and folate metabolism in the cytosol and mitochondria.

One-carbon enters the cytoplasmic folate cycle (green) either through formyltetrahyrofolate synthetase (1) or SHMT (4); MTHFD1 reversibly interconverts 10-CHO-THF to 5,10-CH2-THF by cyclohydrolase (C) and NADP⁺-dependent dehydrogenase (D) activity. 5,10-CH2-THF serves for thymidylate synthesis or is converted by methylenetetrahyrofolate reductase (2) to 5-CH3-THF, which enters the Met cycle (red) and serves for Hcy remethylation to Met by methionine synthase (3) (ref. 17). SAM synthetase (5) converts Met to SAM, which is further converted to SAH (6) during methylation of cytosines, H3K9 and so on. SAH is a competitive inhibitor of methyltransferases (6) and is recycled to Hcy by SAH hydrolase (7) (ref. 23). In mitochondria, one-carbon is transferred to THF during the oxidation of Gly by the glycine decarboxylase complex (8), but surplus of Gly due to photorespiration leads to consumption of one-carbon by SHMT during serine production³⁰. 5-CHO-THF, a byproduct of SHMT, is metabolized by mitochondrial 5-formyltetrahyrofolate cycloligase in order to re-enter the folate cycle (9) (ref. 59). Shuttle of THF between mitochondria and the cytosol has been described in other organisms, but remains uncharacterized in plants.