Multidrug and toxin extrusion transporter (MATE) (MATE)

The multidrug and toxin extrusion (MATE) transporters, specifically MATE1 (SLC47A1) and MATE2-K (SLC47A2), are essential membrane proteins that mediate the final step in the excretion of organic cations from the body (UniProt SLC47A1, SLC47A2). These transporters are primarily localized to the apical membranes of renal proximal tubule cells and the canalicular membrane of hepatocytes, where they function as H+/organic cation antiporters (Motohashi & Inui, 2013). By utilizing the proton gradient, MATE transporters drive the efflux of various xenobiotics and endogenous metabolites into the urine and bile. They are particularly well-known for their role in the renal clearance of metformin, a first-line treatment for type 2 diabetes (Hillgren et al., 2013). Inhibition of MATE transporters by other drugs can lead to significant drug-drug interactions, resulting in increased systemic exposure and potential toxicity of substrate drugs (FDA Guidance, 2020). Because of this clinical relevance, regulatory agencies like the FDA and EMA require the assessment of MATE1 and MATE2-K interaction potential during drug development. Beyond drug disposition, MATE transporters also contribute to the homeostasis of endogenous cations like creatinine and N-methylnicotinamide (Ito et al., 2012).

Other names

SLC47 familySolute carrier family 47MATE1MATE2-KH+/organic cation antiporter

MATE transporters function as H+/organic cation antiporters, utilizing the oppositely directed proton gradient to drive the efflux of organic cations across the apical membrane of epithelial cells into the urine or bile (Motohashi & Inui, 2013).