Adaptation of Monocarboxylate Transporters in Skeletal Muscle

Abstract

Lactate is not an end product of glycolysis but an oxidized substrate in the mitochondria as energy fuel. Lactate transport by monocarboxylate transporter (MCT) plays an important role in lactate utilization. It is reported that MCT1, MCT4 and MCT2 are major subtypes existing in the plasmalemmal and mitochondrial membrane of the skeletal muscle. It has been suggested that these subtypes have different functional roles for monocarboxylate transport. MCT1 predominantly exists in red muscles (slow-oxidative and fast-oxidative fibers) and plays a role in lactate uptake from the circulation to the skeletal muscle. MCT4 predominantly exists in white muscles (fast-glycolytic fibers) and is responsible for the role to release lactate from the muscle outward. It is known that exercise training and chronic muscle contraction can increase muscle MCT1 and MCT4 protein. On the other hand, inactivity, denervation and aging decrease MCT1 and MCT4 protein and lactate transport capacity. Several drugs have extensive effects on MCT1 and MCT4 expression in skeletal muscle. It is likely that MCT2 plays the role to transport pyruvate from the cytosol to the mitochondria in skeletal muscle. The protein expression of MCT1 and MCT4 is regulated partly by peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and hypoxia-inducible factor 1α (HIF-1α), respectively. We discuss about the different adaptation of the MCTs protein expression in skeletal muscle to different physiological stimulus.