Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: Implications for the Cori cycle

doi:10.1016/0092-8674(94)90361-1

Cell

Volume 76, Issue 5, 11 March 1994, Pages 865-873

https://doi.org/10.1016/0092-8674(94)90361-1 Get rights and content

Abstract

Lactate and pyruvate cross cell membranes via a monocarboxylate transporter (MCT) with well-defined properties but undefined molecular structure. We report the cloning of a cDNA encoding MCT1, a monocarboxylate transporter whose properties resemble those of the erythrocyte MCT, including proton symport, trans acceleration, and sensitivity to α-cyanocinammates. A Phe to Cys substitution in MCT1 converts it to Mev, a mevalonate transporter. MCT1 is abundant in erythrocytes, cardiac muscle, and basolateral intestinal epithelium. In skeletal muscle it is restricted to mitochondria-rich myocytes. As sperm traverse the epididymis, MCT1 switches from sperm to epithelial cells. MCT1 is present at low levels in liver, suggesting another MCT in this tissue. By exporting lactate from intestine and erythrocytes, MCT1 participates in the Cori cycle. It also participates in novel pathways of monocarboxylate metabolism in muscle and sperm.

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Abstract

References (27)

Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase

J. Biol. Chem.

Discrimination of three parallel pathways of lactate transport in the human erythrocyte membrane by inhibitors and kinetic properties

Biochem. Biophys.

Expression of specific high capacity mevalonate transport in a Chinese hamster ovary cell variant

J. Biol. Chem.

Eukaryotic proteins expressed in Escherichia coli: an improved thrombin cleavage and purification procedure of fusion proteins with glutathione S-transferase

Anal. Biochem.

The 12-transmembrane helix transporters

Curr. Opin. Cell Biol.

A rabbit erythrocyte membrane protein associated with l-lactate transport

J. Biol. Chem.

cDNA cloning of Mev, a mutant protein that facilitates cellular uptake of mevalonate, and identification of the point mutation responsible for its gain of function

J. Biol. Chem.

Protein measurement with the folin phenol reagent

J. Biol. Chem.

Lactate transport is mediated by a membrane-bound carrier in rat skeletal muscle sarcolemmal vesicles

Arch. Biochem. Biophys.

Transport and Diffusion Across Cell Membranes

Regulation of lactate metabolism in vivo

Diabetes Metab. Rev.

Preferential uptake of lactate by the normal myocardium in dogs

Cardiovasc. Res.

The mechanism of lactate transport in human erythrocytes

J. Membr. Biol.

Cited by (490)

History and Function of the Lactate Receptor GPR81/HCAR1 in the Brain: A Putative Therapeutic Target for the Treatment of Cerebral Ischemia

Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain

The ferredoxin redox system – an essential electron distributing hub in the apicoplast of Apicomplexa

Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state

Lactate, histone lactylation and cancer hallmarks

MCT4-driven CAF-mediated metabolic reprogramming in breast cancer microenvironment is a vulnerability targetable by miR-425-5p