Regulation of the exercise-induced expression of the monocarboxylate transporters MCT1 and MCT4 in skeletal muscle

Abstract

Lactate is a dynamic substrate that has great potential as an energy source. During exercise, lactate is transported out of contracting muscle cells and is oxidized by the heart and oxidative types of muscles. The diffusion of monocarboxylates, such as lactate and pyruvate, across the plasma membranes of mammalian cells is facilitated by a family of integral mem-brane transport proteins called monocarboxylate transporters (MCTs). Currently, 14 unique members of the MCT family have been identified. In skeletal muscle, 2 isoforms with different kinetic properties, MCT1 and MCT4, are expressed and have been identified as key transport-ers regulating lactate flux across the plasma membrane. MCT1 is primarily expressed in oxida-tive fibers, in which lactate can be used as fuel for mitochondrial oxidation, and is closely asso-ciated with the rate of lactate uptake. MCT4 is highly expressed in glycolytic fibers and may be responsible for the removal of lactate produced by glycolysis. Rapid changes in the expression of MCT1 and MCT4 can occur in response to acute exercise, the regulation of which may in-volve transcriptional and post-transcriptional mechanisms. Increased MCT expression may be the primary factor enhancing the rate of lactate flux. However, the molecular regulatory mecha-nisms by which exercise upregulates MCT expression in muscle are not yet fully understood. It is important to understand how exercise regulates MCT expression so that training programs can be designed to increase the muscle oxidative disposal of lactate.