FAD homeostasis in mammalian cells. FAD cofactor is represented in this drawing by a star. Flavin transporters are indicated with circles (circled I, plasma membrane Rf transporter, i.e., RFVT1–3 described in Ref. 12; circled II, mitochondrial Rf transporter, still uncharacterized; circled III, mitochondrial FAD exporter). The question mark indicates the unknown origin of Rf in the nucleus. FAD-synthesizing enzymes are indicated with gray boxes (box 1, riboflavin kinase; box 2, FADS). FAD degrading enzymes are indicated with white boxes (box 3, FAD pyrophosphatase; box 4, FMN phosphohydrolase). Apo-flavoprotein (apo-Fp) into holoflavoprotein (holo-Fp) transition and FAD recycling are indicated with dotted lines. Some nuclear flavoenzymes are indicated with white boxes with a star. AIF, apoptosis inducing factor1; LSD1/2, lysine-specific demethylase 1/2; TXNRD1, thioredoxin reductase. The scheme summarizes the functional studies described in this and other previous papers (18, 61, 62).