Monocarboxylate transporter family (MCT)

The monocarboxylate transporter (MCT) family, primarily belonging to the SLC16 solute carrier group, consists of 14 members that facilitate the proton-linked transport of monocarboxylates such as lactate, pyruvate, and ketone bodies across biological membranes (Halestrap, 2013, Mol Aspects Med). MCT1, MCT2, MCT3, and MCT4 are the most functionally characterized isoforms, playing vital roles in maintaining intracellular pH and metabolic homeostasis by managing the flux of glycolytic end-products (Payen et al., 2020, Mol Metab). In the context of oncology, MCT1 and MCT4 are frequently upregulated to support the Warburg effect, allowing cancer cells to export large quantities of lactate to avoid toxic intracellular acidification (Puri & Juvale, 2020, Eur J Med Chem). This lactate efflux also contributes to the acidification of the tumor microenvironment, which promotes tumor invasion and suppresses anti-tumor immune responses (Beloueche-Babari et al., 2017, Br J Cancer). Therapeutic strategies targeting MCTs, such as the small molecule inhibitor AZD3965, aim to disrupt this metabolic adaptation by inducing metabolic exhaustion and cell death in glycolytic tumors (ClinicalTrials.gov, NCT01791595). Beyond cancer, MCTs are essential for the "lactate shuttle" in the brain and muscles, where they facilitate energy transfer between different cell types (Bergersen, 2007, J Cereb Blood Flow Metab). Mutations in MCT genes are linked to various disorders, including hyperinsulinemic hypoglycemia and erythrocyte lactate transporter deficiency (Halestrap & Wilson, 2012, IUBMB Life). Consequently, the MCT family represents a versatile target for drug development in metabolic diseases, epilepsy, and oncology.

Other names

SLC16 familySolute carrier family 16H+/monocarboxylate transportersProton-linked monocarboxylate transportersSLC16

Inhibition of the transmembrane transport of monocarboxylates, primarily lactate, leading to intracellular acidification and disruption of glycolytic metabolism.