SHMT2 and cancer: In cancer cells, owing to the compartmentalization of one-carbon metabolism, serine is metabolized by the mitochondrial serine hydroxymethyltransferase (SHMT2), bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2/2L), and formyltetrahydrofolate synthetase (MTHFD1L) to produce glycine and formate (Fig. 1).