Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR. (6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + H(+) + NADPH Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1. Expressed in numerous cell lines. Humans have acquired two dihydrofolate reductase enzymes during their evolution, DHFR and DHFR2. In contrast to human, mice and brown rats have just one. Belongs to the dihydrofolate reductase family.