Function and dysfunction of human riboflavin transporters

Riboflavin, otherwise known as vitamin B2, is an essential dietary component and represents the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), the redox enzymatic cofactors required for mitochondrial terminal metabolism and for the functionality of mitochondrial respiratory chain. Protein folding, ROS production and defense, as well as redox epigenetics also depend on cellular supply of FAD [1]. FAD formation in different cells starts from riboflavin uptake, which occurs via specialized carrier-mediated processes which are supported by three specific members of the solute carrier family 52 (SLC52A), identified and named respectively RFVT1, RFVT2 and RFVT3. Alterations of RFVTs have been correlated with rare inherited neuro-muscular disorders, some of which treatable with high doses of the vitamin [2]. To better study structure-function relationships in these human diseases we produced the human RFVT2 transporter by over-expression in E. coli and we reconstituted the purified protein in proteoliposomes for transport assay. We also pointed our attention on a profound alteration of flavin cofactor homeostasis in human colorectal [3] and some other types of cancer, which are accompanied by dysregulation of RFVTs expression. Changing the level of RFVTs expression as a possible mean to reprogram flavoproteome will be discussed.