Skip to main content
SpringerLink
Log in

Molecular Characteristics, Regulation, and Function of Monocarboxylate Transporters

  • Chapter
  • First Online:
Glial Amino Acid Transporters

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 16))

Abstract

Lactate transporters play an important role in the glutamate recycling. Here their kinetics and tissue distribution with emphasis on the brain are addressed. Recent evidence shows their participation in important brain functions that involve intercellular communication, such as hypothalamic glucose sensing. Furthermore, we describe the regulation of their expression and some animal models that have allowed clarification of their functions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

[Ca2+]i :

Intracellular calcium concentrations

3V:

Third ventricle

4-CIN:

4-hydroxycinnamate

ALS:

Amyotrophic lateral sclerosis

AMP:

Adenosine monophosphate

AMPK:

Protein kinase activated by AMP

AN:

Arcuate nucleus

ATP:

Adenosine triphosphate

DEPC:

Diethyl pyrocarbonate

DIDS:

4,4-di-isotiocianoestibeno acid -2,2-disulfonic

DMN:

Dorsomedial nucleus

DNA:

Deoxyribonucleic acid

GFAP:

Glial fibrillary acidic protein

GLAST:

Glutamate aspartate transporter

GLT-1:

Glutamate transporter 1 (GLT-1)

GLUT4:

Glucose transporter type 4

HIF-1α:

Hypoxia-inducible factor 1-α

HUGO:

Human Genome Organization

IGF-1:

Insulin-like growth factor 1

MCTs:

Monocarboxylate transporters

mTOR:

AKT kinase and mechanistic target of rapamycin

NFAT:

Nuclear factor of activated T cells

NPY:

Neuropeptide Y

pCMB:

P-chloromercuribenzene sulfonate

PEPCK:

Phosphoenolpyruvate carboxykinase

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

PVN:

Paraventricular nucleus

T3:

Triiodothyronine

TM:

Transmembrane

References

  • Ainscow EK, Mirshamsi S, Tang T, Ashford ML, Rutter GA. Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones: evidence for ATP-independent control of ATP-sensitive K(+) channels. J Physiol. 2002;544(Pt 2):429–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson CM, Swanson RA. Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia. 2000;32(1):1–14.

    Article  CAS  PubMed  Google Scholar 

  • Benton CR, Yoshida Y, Lally J, Han X-X, Hatta H, Bonen A. PGC-1α increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4. Physiol Genomics. 2008;35(1):45–54.

    Article  CAS  PubMed  Google Scholar 

  • Bergersen LH. Is lactate food for neurons? Comparison of monocarboxylate transporter subtypes in brain and muscle. Neuroscience. 2007;145(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  • Bergersen L, Johannsson E, Veruki ML, Nagelhus EA, Halestrap A, Sejersted OM, Ottersen OP. Cellular and subcellular expression of monocarboxylate transporters in the pigment epithelium and retina of the rat. Neuroscience. 1999;90(1):319–31.

    Article  CAS  PubMed  Google Scholar 

  • Bergersen L, Waerhaug O, Helm J, Thomas M, Laake P, Davies AJ, Wilson MC, Halestrap AP, Ottersen OP. A novel postsynaptic density protein: the monocarboxylate transporter MCT2 is co-localized with delta-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses. Exp Brain Res. 2001;136(4):523–34.

    Article  CAS  PubMed  Google Scholar 

  • Bigard X, Sanchez H, Zoll J, Mateo P, Rousseau V, Veksler V, Ventura-Clapier R. Calcineurin co-regulates contractile and metabolic components of slow muscle phenotype. J Biol Chem. 2000;275(26):19653–60.

    Article  CAS  PubMed  Google Scholar 

  • Bogan JS. Regulation of glucose transporter translocation in health and diabetes. Annu Rev Biochem. 2012;81:507–32.

    Article  CAS  PubMed  Google Scholar 

  • Broer S, Rahman B, Pellegri G, Pellerin L, Martin JL, Verleysdonk S, Hamprecht B, Magistretti PJ. Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons. J Biol Chem. 1997;272(48):30096–102.

    Article  CAS  PubMed  Google Scholar 

  • Broer S, Schneider HP, Broer A, Rahman B, Hamprecht B, Deitmer JW. Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem J. 1998;333(Pt 1):167–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW. Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999;341(Pt 3):529–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Canis M, Maurer MH, Kuschinsky W, Duembgen L, Duelli R. Increased densities of monocarboxylate transporter MCT1 after chronic hyperglycemia in rat brain. Brain Res. 2009;1257:32–9.

    Article  CAS  PubMed  Google Scholar 

  • Carneiro L, Pellerin L. Monocarboxylate transporters: new players in body weight regulation. Obes Rev. 2015;16(Suppl 1):55–66.

    Article  PubMed  Google Scholar 

  • Carneiro L, Geller S, Fioramonti X, Hebert A, Repond C, Leloup C, Pellerin L. Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice. Am J Physiol Endocrinol Metab. 2016;310(2):E103–15.

    PubMed  Google Scholar 

  • Carpenter L, Halestrap AP. The kinetics, substrate and inhibitor specificity of the lactate transporter of Ehrlich-Lettre tumour cells studied with the intracellular pH indicator BCECF. Biochemical Journal. 1994;304(3):751–760.

    Google Scholar 

  • Cortes-Campos C, Elizondo R, Llanos P, Uranga RM, Nualart F, Garcia MA. MCT expression and lactate influx/efflux in tanycytes involved in glia-neuron metabolic interaction. PLoS One. 2011;6(1):e16411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cortes-Campos C, Elizondo R, Carril C, Martinez F, Boric K, Nualart F, Garcia-Robles MA. MCT2 expression and lactate influx in anorexigenic and orexigenic neurons of the arcuate nucleus. PLoS One. 2013;8(4):e62532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cremer JE. Substrate utilization and brain development. J Cereb Blood Flow Metab. 1982;2(4):394–407.

    Article  CAS  PubMed  Google Scholar 

  • Chenal J, Pellerin L. Noradrenaline enhances the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of PI3K/Akt and the mTOR/S6K pathway. J Neurochem. 2007;102(2):389–97.

    Article  CAS  PubMed  Google Scholar 

  • Chenal J, Pierre K, Pellerin L. Insulin and IGF-1 enhance the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin pathway. Eur J Neurosci. 2008;27(1):53–65.

    Article  PubMed  Google Scholar 

  • Chiry O, Fishbein WN, Merezhinskaya N, Clarke S, Galuske R, Magistretti PJ, Pellerin L. Distribution of the monocarboxylate transporter MCT2 in human cerebral cortex: an immunohistochemical study. Brain Res. 2008;1226:61–9.

    Article  CAS  PubMed  Google Scholar 

  • Dimmer KS, Friedrich B, Lang F, Deitmer JW, Broer S. The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem J. 2000;350(Pt 1):219–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dombrowski GJ Jr, Swiatek KR, Chao KL. Lactate, 3-hydroxybutyrate, and glucose as substrates for the early postnatal rat brain. Neurochem Res. 1989;14(7):667–75.

    Article  CAS  PubMed  Google Scholar 

  • Elizondo-Vega R, Cortes-Campos C, Barahona MJ, Oyarce KA, Carril CA, Garcia-Robles MA. The role of tanycytes in hypothalamic glucosensing. J Cell Mol Med. 2015;19(7):1471–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elizondo-Vega R, Cortes-Campos C, Barahona MJ, Carril C, Ordenes P, Salgado M, Oyarce K, Garcia-Robles ML. Inhibition of hypothalamic MCT1 expression increases food intake and alters orexigenic and anorexigenic neuropeptide expression. Sci Rep. 2016;6:33606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ. Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem. 2003;278(41):40128–35.

    Article  CAS  PubMed  Google Scholar 

  • Garcia CK, Brown MS, Pathak RK, Goldstein JL. cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1. J Biol Chem. 1995;270(4):1843–9.

    Article  CAS  PubMed  Google Scholar 

  • Gerhart DZ, Enerson BE, Zhdankina OY, Leino RL, Drewes LR. Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats. Am J Phys. 1997;273(1 Pt 1):E207–13.

    CAS  Google Scholar 

  • Gerhart DZ, Enerson BE, Zhdankina OY, Leino RL, Drewes LR. Expression of the monocarboxylate transporter MCT2 by rat brain glia. Glia. 1998;22(3):272–281.

    Google Scholar 

  • Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol. 2004;558(Pt 1):5–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grollman EF, Philp NJ, McPhie P, Ward RD, Sauer B. Determination of transport kinetics of chick MCT3 monocarboxylate transporter from retinal pigment epithelium by expression in genetically modified yeast. Biochemistry. 2000;39(31):9351–7.

    Article  CAS  PubMed  Google Scholar 

  • Halestrap AP. The monocarboxylate transporter family – structure and functional characterization. IUBMB Life. 2012;64(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  • Halestrap AP. Monocarboxylic acid transport. Compr Physiol. 2013a;3(4):1611–43.

    Article  PubMed  Google Scholar 

  • Halestrap AP. The SLC16 gene family – structure, role and regulation in health and disease. Mol Asp Med. 2013b;34(2–3):337–49.

    Article  CAS  Google Scholar 

  • Halestrap AP, Price NT. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J. 1999;343(Pt 2):281–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halestrap AP, Wang X, Poole RC, Jackson VN, Price NT. Lactate transport in heart in relation to myocardial ischemia. Am J Cardiol. 1997;80(3A):17A–25A.

    Article  CAS  PubMed  Google Scholar 

  • Hanu R, McKenna M, O’Neill A, Resneck WG, Bloch RJ. Monocarboxylic acid transporters, MCT1 and MCT2, in cortical astrocytes in vitro and in vivo. Am J Physiol Cell Physiol. 2000;278(5):C921–30.

    CAS  PubMed  Google Scholar 

  • Hatta H, Tonouchi M, Miskovic D, Wang Y, Heikkila JJ, Bonen A. Tissue-specific and isoform-specific changes in MCT1 and MCT4 in heart and soleus muscle during a 1-yr period. Am J Physiol Endocrinol Metab. 2001;281(4):E749–56.

    CAS  PubMed  Google Scholar 

  • Hawkins RA, Williamson DH, Krebs HA. Ketone-body utilization by adult and suckling rat brain in vivo. Biochem J. 1971;122(1):13–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hawkins RA, Mans AM, Davis DW. Regional ketone body utilization by rat brain in starvation and diabetes. Am J Phys. 1986;250(2 Pt 1):E169–78.

    CAS  Google Scholar 

  • Hugo SE, Cruz-Garcia L, Karanth S, Anderson RM, Stainier DY, Schlegel A. A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting. Genes Dev. 2012;26(3):282–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwata K, Kinoshita M, Yamada S, Imamura T, Uenoyama Y, Tsukamura H, Maeda K. Involvement of brain ketone bodies and the noradrenergic pathway in diabetic hyperphagia in rats. J Physiol Sci. 2011;61(2):103–13.

    Article  CAS  PubMed  Google Scholar 

  • Jackson VN, Halestrap AP. The kinetics, substrate, and inhibitor specificity of the monocarboxylate (lactate) transporter of rat liver cells determined using the fluorescent intracellular pH indicator, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. J Biol Chem. 1996;271(2):861–8.

    Article  CAS  PubMed  Google Scholar 

  • Johannsson E, Lunde PK, Heddle C, Sjaastad I, Thomas MJ, Bergersen L, Halestrap AP, Blackstad TW, Ottersen OP, Sejersted OM. Upregulation of the cardiac monocarboxylate transporter MCT1 in a rat model of congestive heart failure. Circulation. 2001;104(6):729–34.

    Article  CAS  PubMed  Google Scholar 

  • Kim DK, Kanai Y, Matsuo H, Kim JY, Chairoungdua A, Kobayashi Y, Enomoto A, Cha SH, Goya T, Endou H. The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. Genomics. 2002;79(1):95–103.

    Article  CAS  PubMed  Google Scholar 

  • Koehler-Stec EM, Simpson IA, Vannucci SJ, Landschulz KT, Landschulz WH. Monocarboxylate transporter expression in mouse brain. Am J Phys. 1998;275(3 Pt 1):E516–24.

    CAS  Google Scholar 

  • Lam CK, Chari M, Wang PY, Lam TK. Central lactate metabolism regulates food intake. Am J Physiol Endocrinol Metab. 2008;295(2):E491–6.

    Article  CAS  PubMed  Google Scholar 

  • Lee WJ, Kim M, Park HS, Kim HS, Jeon MJ, Oh KS, Koh EH, Won JC, Kim MS, Oh GT, Yoon M, Lee KU, Park JY. AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1. Biochem Biophys Res Commun. 2006;340(1):291–5.

    Article  CAS  PubMed  Google Scholar 

  • Lee Y, Morrison BM, Li Y, Lengacher S, Farah MH, Hoffman PN, Liu Y, Tsingalia A, Jin L, Zhang PW, Pellerin L, Magistretti PJ, Rothstein JD. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature. 2012;487(7408):443–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leino RL, Gerhart DZ, Drewes LR. Monocarboxylate transporter (MCT1) abundance in brains of suckling and adult rats: a quantitative electron microscopic immunogold study. Brain Res Dev Brain Res. 1999;113(1–2):47–54.

    Article  CAS  PubMed  Google Scholar 

  • Leino RL, Gerhart DZ, Duelli R, Enerson BE, Drewes LR. Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain. Neurochem Int. 2001;38(6):519–27.

    Article  CAS  PubMed  Google Scholar 

  • Lengacher S, Nehiri-Sitayeb T, Steiner N, Carneiro L, Favrod C, Preitner F, Thorens B, Stehle JC, Dix L, Pralong F, Magistretti PJ, Pellerin L. Resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice. PLoS One. 2013;8(12):e82505.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin RY, Vera JC, Chaganti RS, Golde DW. Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter. J Biol Chem. 1998;273(44):28959–65.

    Article  CAS  PubMed  Google Scholar 

  • Magistretti PJ, Pellerin L. Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond Ser B Biol Sci. 1999;354(1387):1155–63.

    Article  CAS  Google Scholar 

  • Manning Fox JE, Meredith D, Halestrap AP. Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J Physiol. 2000;529(Pt 2):285–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuyama S, Ohkura S, Iwata K, Uenoyama Y, Tsukamura H, Maeda K, Kimura K. Food deprivation induces monocarboxylate transporter 2 expression in the brainstem of female rat. J Reprod Dev. 2009;55(3):256–61.

    Article  CAS  PubMed  Google Scholar 

  • Meredith D, Bell P, McClure B, Wilkins R. Functional and molecular characterisation of lactic acid transport in bovine articular chondrocytes. Cell Physiol Biochem. 2002;12(4):227–34.

    Article  CAS  PubMed  Google Scholar 

  • Murakami Y, Kohyama N, Kobayashi Y, Ohbayashi M, Ohtani H, Sawada Y, Yamamoto T. Functional characterization of human monocarboxylate transporter 6 (SLC16A5). Drug Metab Dispos. 2005;33(12):1845–51.

    CAS  PubMed  Google Scholar 

  • Murray CM, Hutchinson R, Bantick JR, Belfield GP, Benjamin AD, Brazma D, Bundick RV, Cook ID, Craggs RI, Edwards S, Evans LR, Harrison R, Holness E, Jackson AP, Jackson CG, Kingston LP, Perry MW, Ross AR, Rugman PA, Sidhu SS, Sullivan M, Taylor-Fishwick DA, Walker PC, Whitehead YM, Wilkinson DJ, Wright A, Donald DK. Monocarboxylate transporter MCT1 is a target for immunosuppression. Nat Chem Biol. 2005;1(7):371–6.

    Article  CAS  PubMed  Google Scholar 

  • Ojuka EO. Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle. Proc Nutr Soc. 2004;63(2):275–8.

    Article  CAS  PubMed  Google Scholar 

  • Ovens MJ, Davies AJ, Wilson MC, Murray CM, Halestrap AP. AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7–10. Biochem J. 2010a;425(3):523–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ovens MJ, Manoharan C, Wilson MC, Murray CM, Halestrap AP. The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein. Biochem J. 2010b;431(2):217–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pellerin L, Magistretti PJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A. 1994;91(22):10625–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pellerin L, Bergersen LH, Halestrap AP, Pierre K. Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain. J Neurosci Res. 2005;79(1–2):55–64.

    Article  CAS  Google Scholar 

  • Perez de Heredia F, Wood IS, Trayhurn P. Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes. Pflugers Arch. 2010;459(3):509–18.

    Article  CAS  PubMed  Google Scholar 

  • Philp NJ, Ochrietor JD, Rudoy C, Muramatsu T, Linser PJ. Loss of MCT1, MCT3, and MCT4 expression in the retinal pigment epithelium and neural retina of the 5A11/basigin-null mouse. Invest Ophthalmol Vis Sci. 2003;44(3):1305–11.

    Article  PubMed  Google Scholar 

  • Pierre K, Pellerin L. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. J Neurochem. 2005;94(1):1–14.

    Article  CAS  PubMed  Google Scholar 

  • Pierre K, Pellerin L, Debernardi R, Riederer BM, Magistretti PJ. Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy. Neuroscience. 2000;100(3):617–27.

    Article  CAS  PubMed  Google Scholar 

  • Pierre K, Parent A, Jayet PY, Halestrap AP, Scherrer U, Pellerin L. Enhanced expression of three monocarboxylate transporter isoforms in the brain of obese mice. J Physiol. 2007;583(Pt 2):469–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poole RC, Halestrap AP. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am J Phys. 1993;264(4 Pt 1):C761–82.

    CAS  Google Scholar 

  • Pullen TJ, da Silva Xavier G, Kelsey G, Rutter GA. miR-29a and miR-29b contribute to pancreatic beta-cell-specific silencing of monocarboxylate transporter 1 (Mct1). Mol Cell Biol. 2011;31(15):3182–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rafiki A, Boulland JL, Halestrap AP, Ottersen OP, Bergersen L. Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain. Neuroscience. 2003;122(3):677–88.

    Article  CAS  PubMed  Google Scholar 

  • Sonnewald U. Glutamate synthesis has to be matched by its degradation – where do all the carbons go? J Neurochem. 2014;131(4):399–406.

    Article  CAS  PubMed  Google Scholar 

  • Suhre K, Shin SY, Petersen AK, Mohney RP, Meredith D, Wagele B, Altmaier E, CardioGram, Deloukas P, Erdmann J, Grundberg E, Hammond CJ, de Angelis MH, Kastenmuller G, Kottgen A, Kronenberg F, Mangino M, Meisinger C, Meitinger T, Mewes HW, Milburn MV, Prehn C, Raffler J, Ried JS, Romisch-Margl W, Samani NJ, Small KS, Wichmann HE, Zhai G, Illig T, Spector TD, Adamski J, Soranzo N, Gieger C. Human metabolic individuality in biomedical and pharmaceutical research. Nature. 2011;477(7362):54–60.

    Article  CAS  PubMed  Google Scholar 

  • Takimoto M, Hamada T. Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins. J Appl Physiol (1985). 2014;116(9):1238–50.

    Article  CAS  Google Scholar 

  • Tarczyluk MA, Nagel DA, Rhein Parri H, Tse EH, Brown JE, Coleman MD, Hill EJ. Amyloid beta 1-42 induces hypometabolism in human stem cell-derived neuron and astrocyte networks. J Cereb Blood Flow Metab. 2015;35(8):1348–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ullah MS, Davies AJ, Halestrap AP. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem. 2006;281(14):9030–7.

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Tonouchi M, Miskovic D, Hatta H, Bonen A. T3 increases lactate transport and the expression of MCT4, but not MCT1, in rat skeletal muscle. Am J Physiol Endocrinol Metab. 2003;285(3):E622–8.

    Article  CAS  PubMed  Google Scholar 

  • Wilson MC, Jackson VN, Heddle C, Price NT, Pilegaard H, Juel C, Bonen A, Montgomery I, Hutter OF, Halestrap AP. Lactic acid efflux from white skeletal muscle is catalyzed by the monocarboxylate transporter isoform MCT3. J Biol Chem. 1998;273(26):15920–6.

    Article  CAS  PubMed  Google Scholar 

  • Wilson MC, Meredith D, Fox JE, Manoharan C, Davies AJ, Halestrap AP. Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4: the ancillary protein for the insensitive MCT2 is EMBIGIN (gp70). J Biol Chem. 2005;280(29):27213–21.

    Article  CAS  PubMed  Google Scholar 

  • Yoon H, Donoso LA, Philp NJ. Cloning of the human monocarboxylate transporter MCT3 gene: localization to chromosome 22q12.3-q13.2. Genomics. 1999;60(3):366–70.

    Article  CAS  PubMed  Google Scholar 

  • Zhao C, Wilson MC, Schuit F, Halestrap AP, Rutter GA. Expression and distribution of lactate/monocarboxylate transporter isoforms in pancreatic islets and the exocrine pancreas. Diabetes. 2001;50(2):361–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Biología Celular, Universidad de Concepción, Concepción, Chile

    Roberto Elizondo-Vega & María Angeles García-Robles

Authors
  1. Roberto Elizondo-Vega
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. María Angeles García-Robles
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to María Angeles García-Robles .

Editor information

Editors and Affiliations

  1. Department of Toxicology, Cinvestav-IPN México City, México, Mexico

    Arturo Ortega

  2. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Arne Schousboe

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Elizondo-Vega, R., García-Robles, M.A. (2017). Molecular Characteristics, Regulation, and Function of Monocarboxylate Transporters. In: Ortega, A., Schousboe, A. (eds) Glial Amino Acid Transporters. Advances in Neurobiology, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-319-55769-4_12

Download citation

Publish with us

Policies and ethics

Search

Navigation