Human riboflavin transporters in health and diseases

Riboflavin, otherwise known as vitamin B2, is an essential dietary component and it represents the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), the redox enzymatic cofactors required for hundreds of enzymes involved in protein folding, apoptosis, epigenetics and mitochondrial terminal metabolism [1]. Flavin cofactor biosynthesis 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. We pointed our attention on a profound alteration of flavin cofactor homeostasis in human colorectal [2] 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 cellular flavoproteome will be discussed. Primary or secondary alterations of the activity/expression of RFVTs have been correlated with rare inherited neuro-muscular disorders, some of which treatable with high doses of the vitamin [3]. The effect of alteration of flavin cofactor availability on mitochondrial flavoenzymes in human cells and worm models will be discussed. To better study structure-function relationships in these human diseases over-production of the human RFVT2 transporter in E. coli was carried out and reconstitution of the purified protein in proteoliposomes for transport assay was performed.