The SLC16A Family of Monocarboxylate Transporters (MCTs)—Physiology and Function in Cellular Metabolism, pH Homeostasis, and Fluid Transport

Abstract The SLC16A family of monocarboxylate transporters (MCTs) is composed of 14 members. MCT1 through MCT4 (MCTs 1–4) are H + -coupled monocarboxylate transporters, MCT8 and MCT10 transport thyroid hormone and aromatic amino acids, while the substrate specificity and function of other MCTs have yet to be determined. The focus of this review is on MCTs 1–4 because their role in lactate transport is intrinsically linked to cellular metabolism in various biological systems, including skeletal muscle, brain, retina, and testis. Although MCTs 1–4 all transport lactate, they differ in their transport kinetics and vary in tissue and subcellular distribution, where they facilitate “lactate-shuttling” between glycolytic and oxidative cells within tissues and across blood–tissue barriers. However, the role of MCTs 1–4 is not confined to cellular metabolism. By interacting with bicarbonate transport proteins and carbonic anhydrases, MCTs participate in the regulation of pH homeostasis and fluid transport in renal proximal tubule and corneal endothelium, respectively. Here, we provide a comprehensive review of MCTs 1–4, linking their cellular distribution to their functions in various parts of the human body, so that we can better understand the physiological roles of MCTs at the systemic level.