The monocarboxylate transporter familyuRole and regulation

被引:527
作者
Halestrap, Andrew P. [1 ]
Wilson, Marieangela C. [1 ]
机构
[1] Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England
关键词
lactate; pyruvate; metabolism; cancer; cell cycle; MCT; basigin; hypoxia; MITOCHONDRIAL PYRUVATE CARRIER; THYROID-HORMONE TRANSPORTER; CARBONIC-ANHYDRASE II; LACTATE TRANSPORT; PIGMENT-EPITHELIUM; SKELETAL-MUSCLE; MCT1; EXPRESSION; CELLS; RAT;
D O I
10.1002/iub.572
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Monocarboxylate transporter (MCT) isoforms 14 catalyze the proton-linked transport of monocarboxylates such as L-lactate across the plasma membrane, whereas MCT8 and MCT10 are thyroid hormone and aromatic amino acid transporters, respectively. The importance of MCTs is becoming increasingly evident as their extensive physiological and pathological roles are revealed. MCTs 14 play essential metabolic roles in most tissues with their distinct properties, expression profile, and subcellular localization matching the particular metabolic needs of a tissue. Important metabolic roles include energy metabolism in the brain, skeletal muscle, heart, tumor cells, and T-lymphocyte activation, gluconeogenesis in the liver and kidney, spermatogenesis, bowel metabolism of short-chain fatty acids, and drug transport. MCT8 is essential for thyroid hormone transport across the bloodbrain barrier. Genetic perturbation of MCT function may be involved in disease states such as pancreatic beta-cell malfunction (inappropriate MCT1 expression), chronic fatigue syndromes (impairment of muscle MCT function), and psychomotor retardation (MCT8 mutation). MCT expression can be regulated at both the transcriptional and post-transcriptional levels. Of particular importance is the upregulation of muscle MCT1 expression in response to training and MCT4 expression in response to hypoxia. The latter is mediated by hypoxia inducible factor 1a and often observed in tumor cells that rely almost entirely on glycolysis for their energy provision. The recent discovery of potent and specific MCT1 inhibitors that prevent proliferation of T-lymphocytes confirms that MCTs may be promising pharmacological targets including for cancer chemotherapy. (c) 2011 IUBMB IUBMB Life, 2011.
引用
收藏
页码:109 / 119
页数:11
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