Across different cancer cell lines, cytoplasmic and mitochondrial [NADPH] were shown to positively correlate with NNT gene expression, while a negative correlation was found between mitochondrial [NADPH] and MTHFD1 expression [105], which is not surprising given that MTHFD1 oxidizes cytoplasmic NADPH in over half of all cell lines tested due to the specific direction of folate cycle flux established by the preferential serine catabolism by mitochondrial matrix SHMT2 compared to that of cytoplasmic serine hydroxymethyltransferase 1 (SHMT1) [19,106]. The gene discussed is MTHFD1; the disease is cancer.