monocarboxylaattransporters

Monocarboxylate transporters (MCTs) are a family of membrane transport proteins encoded by the SLC16 gene family that mediate the proton-linked transport of monocarboxylates across the plasma membrane. The primary substrates include lactate, pyruvate, and ketone bodies such as acetoacetate and beta-hydroxybutyrate. Transport is typically bidirectional and driven by the combined gradients of the monocarboxylate and the proton, enabling cells to import or export these metabolites as part of cellular energy and pH regulation.

The best characterized members are MCT1 (SLC16A1), MCT2 (SLC16A7), MCT3 (SLC16A8), and MCT4 (SLC16A3). MCT1 is widely expressed and supports lactate/pyruvate exchange in many tissues; MCT2 has a higher affinity for lactate and is enriched in brain and some neurons; MCT4 is highly expressed in glycolytic tissues such as skeletal muscle and adipocytes, where it primarily mediates lactate export. MCT3 expression is more restricted, including retina and certain epithelia. Most MCTs require accessory proteins to reach the cell surface, notably basigin (CD147) for several isoforms and embigin for others, functioning as chaperones that promote proper trafficking and activity.

Physiological roles include lactate shuttling between cells and tissues, such as the astrocyte–neuron lactate shuttle in the brain, lactate export from exercising muscle, and lactate uptake by oxidative tissues. In pathology, increased glycolysis in cancer often elevates extracellular lactate, with MCTs aiding export and contributing to the tumor microenvironment. Regulation of MCT expression is influenced by hypoxia and metabolic cues, with hypoxia-inducible factors upregulating MCT4 in many contexts.

Clinically, MCTs are explored as therapeutic targets in cancer and metabolic disorders. Inhibitors such as CHC and AZD3965 (MCT1 inhibitor) are used in research and development to probe transport roles and therapeutic potential.