Abstract

Solute Carrier (SLC) transporters mediate the translocation of substrates across membranes and after GPC Rs represent the second-largest fraction of the human membrane proteome. SLC transporters are critical to cell homeostasis, which is reflected in the fact that more than a quarter of them are associated with Mendelian disease. Despite a few exceptions, however, they have been under-utilized as drug targets and our mechanistic understanding has been hampered due to technical difficulties in working with them. Here, I will present our multidisciplinary approach that has revealed important insights into the mechanism of SLC2 (GLUT) and SLC9 (Na+/H+ exchanger) transporter families that are important for our cells to utilize glucose as an energy source, and for the regulation cytoplasmic and organellar pH. I will also present our most recent biochemical and structural insights into ADP /ATP exchanger belonging to the SLC35 (nucleotide-sugar) family, which is essential for the uptake of ATP into ER and Golgi organelles for a number of biological processes, such as protein-folding.