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In polarized cells, Mate/MATE transporters localize to apical surfaces including hepatic canalicular and tubular brush border membranes (Fig. 3.2) [5, 6, 23]. This localization coupled with the lower pH of luminal spaces leads to the secretion of organic cations in vivo. Sequestration of organic cations in intracellular vesicles or endosomes can also be accomplished by MATE1 working in concert with the V‐type H⁺‐ATPase [24]. While these MATE1‐expressing endosomes may alter the intracellular distribution of organic cations, they do not appear to influence the subsequent apical efflux. In other cell types, such as serous and mucous acinar cells and duct cells, MATE1 protein can be observed on both the apical and basolateral membranes [8].

FIGURE 3.1 Mate transporters across species and localization. (a) Phylogenic tree of MATE transporters in mammals according to three subclasses: class I (red), class II (black), and class III (blue).

Adapted from [22].

(b) Transepithelial transport by OCT and MATE proteins in liver (left) and kidneys (right).