MCT1

Monocarboxylate transporter 1 (MCT1) is a proton-linked transporter encoded by the SLC16A1 gene and is part of the monocarboxylate transporter family (MCT1–MCT4). The protein is a multi-pass membrane protein with about 12 transmembrane domains and relies on chaperone proteins such as basigin (CD147) or embigin to reach the plasma membrane. In the cell membrane, MCT1 mediates the bidirectional transport of monocarboxylates, notably lactate, pyruvate, and ketone bodies, in a proton-coupled manner. Transport direction and rate are determined by substrate concentrations and extracellular pH, supporting intercellular lactate shuttling between glycolytic and oxidative tissues.

MCT1 is broadly expressed, with particularly high levels in skeletal muscle, heart, and brain endothelium, and detectable expression in erythrocytes and various cancer cells. In the brain, MCT1 participates in lactate transport across the blood–brain barrier and in neuron–astrocyte lactate shuttling, contributing to cerebral energy metabolism. In peripheral tissues, it enables lactate efflux from glycolytic cells and lactate uptake by cells that can oxidize lactate for energy.

Regulation of MCT1 expression and activity is linked to cellular metabolic state and tissue-specific factors. Clinically, MCT1 is of interest in cancer biology because many tumors rely on lactate export to maintain glycolytic metabolism; inhibitors of MCT1, such as AZD3965, have been developed and evaluated in research and clinical contexts. CHC (alpha-cyano-4-hydroxycinnamate) is a broader, less selective inhibitor used in experimental studies. Defects or altered regulation of MCT1 can impair lactate transport and affect cellular energy homeostasis.