Multidrug and toxic compound extrusion transporter (MATE)

Multidrug and toxic compound extrusion (MATE) transporters, specifically MATE1 (SLC47A1) and MATE2-K (SLC47A2), are critical solute carriers responsible for the final step in the renal and biliary excretion of organic cations and xenobiotics (UniProt Q96FL8, Q86VL8). Located on the apical membranes of renal proximal tubule cells and the canalicular membrane of hepatocytes, they function as H+/organic cation antiporters that drive the efflux of substrates into the urine or bile using an oppositely directed proton gradient (PMID: 21115604). These transporters are of significant clinical importance because they mediate the clearance of widely prescribed drugs, most notably the anti-diabetic agent metformin (PMID: 23133169). Inhibition of MATE transporters by co-administered drugs like cimetidine or dolutegravir can lead to clinically significant drug-drug interactions, resulting in elevated plasma levels of substrates and potential toxicity (FDA Guidance on Drug Interactions). Furthermore, because MATE transporters also handle the secretion of creatinine, their inhibition can cause a benign increase in serum creatinine levels, which may be misinterpreted as a decline in glomerular filtration rate (PMID: 22955152). Understanding MATE activity is essential for predicting drug disposition and managing safety profiles in polypharmacy settings.

Other names

SLC47 familySolute carrier family 47MATE1MATE2-KH+/organic cation antiporterSLC47A1SLC47A2

Inhibition of transporter-mediated efflux leading to increased systemic drug exposure; substrate for renal and biliary excretion via H+/organic cation exchange.