Monokarboksil Taşıyıcı Proteinler ve Egzersizdeki Rolü

Yıl 2024, Cilt: 19 Sayı: 2, 387 - 411, 31.07.2024

Ahmet Bayrak , Suleyman Patlar , Levent Ziya Bulut

https://doi.org/10.33459/cbubesbd.1437354

Öz

Laktik asit, iskelet kasları için başlıca enerji kaynağı (oksidatif fibrillerde) olmasının yanında glikoliz sürecinde oluşan son ürün olarak işlevde görür (glikolitik fibrillerde). Hücre içine ve dışına taşınımı için de özel bir taşınma mekanizmasına ihtiyaç vardır. İskelet kasının plazma (sarkolemmal) zarlarında iki laktat/proton yardımcı taşıyıcı izoformu (monokarboksilat taşıyıcılar, MCT1 ve MCT4) bulunur. Her iki izoform da hem kas pH'ında hem de laktat regülasyonunda yer alır. Buna göre sarkolemmal MCT izoform ekspresyonu, egzersiz performansında önemli bir rol oynayabilir. Akut egzersiz, egzersizin başlangıcından itibaren ilk 24 saat içinde insan MCT içeriğini değiştirir. Kronik egzersiz, deneklerin başlangıçtaki uygunluğundan bağımsız olarak MCT1 ve MCT4 içeriğini de etkiler. Kesitsel çalışmalara göre, yoğunluk MCT içeriğindeki egzersize bağlı değişiklikleri düzenleyen en önemli faktör gibi görünmektedir. MCT içeriğinin düzenlenmesi ile laktat taşıma aktivitesi arasındaki ayrışma, bir dizi çalışmada rapor edilmiştir. MCT içeriğindeki değişiklikler kontraktil aktiviteye yanıt olarak, laktat taşıma kapasitesindeki değişiklikler ise metabolik yollardaki değişikliklere yanıt olarak ortaya çıkar. Kas MCT ifadesi, fiziksel aktivite sırasında kas H(+) ve laktat(-) anyon değişiminde yer alır, ancak bunların tek belirleyicisi değildir. İskelet kası MCT1 ve MCT4 içeriğinin, laktat seviyesinin yükselmesine neden olan egzersiz, hipoksi, beslenme ve metabolik düzensizlikler gibi çeşitli uyaranlarla düzenlendiği bildirilmiştir. Bu derlemenin amacı, egzersizin MCT proteinleri üzerindeki etkileri ile MCT proteinleri sportif performans ilişkisinin yeni literatürler ışığında belirlenmesidir.

Anahtar Kelimeler

MCT, Egzersiz, Laktat, Performans

Monocarboxylate Transporters and Their Role in Exercise

Öz

Lactic acid serves as both the main fuel (oxidative fibers) and the end product (glycolytic fibers) for skeletal muscles. A specialized transport mechanism is required for its movement into and out of cells. Within the plasma (sarcolemma) membranes of skeletal muscles, two lactate/proton co-transporter isoforms (monocarboxylate transporters, MCT1 and MCT4) are present. Both isoforms are involved in regulating muscle pH and lactate levels. Accordingly, sarcolemmal MCT isoform expression could play a significant role in exercise performance. Acute exercise modifies human MCT content within the first 24 hours from the onset of exercise. Chronic exercise affects MCT1 and MCT4 content regardless of initial fitness levels. According to cross-sectional studies, exercise intensity appears to be a crucial factor regulating changes in MCT content. Discrepancies between MCT content regulation and lactate transport activity have been reported in several studies. Changes in MCT content emerge in response to contractile activity, while alterations in lactate transport capacity arise in response to changes in metabolic pathways. Muscle MCT expression participates in the exchange of H(+) and lactate(-) ions during physical activity, although it is not their sole determinant. The content of MCT1 and MCT4 in skeletal muscles has been reported to be regulated by various stimuli, including exercise, hypoxia, nutrition, and metabolic disruptions, all of which lead to elevated lactate levels. The purpose of this review is to elucidate the effects of exercise on MCT proteins and their relationship to sports performance based on recent literature.

Anahtar Kelimeler

MCT, Exercise, Lactic acid, Performance

Kaynakça

• Adijanto, J., & Philp, N. J. (2012). The SLC16A family of monocarboxylate transporters (MCTs)—physiology and function in cellular metabolism, pH homeostasis, and fluid transport. Current Topics in. Membranes, 70, 275–311. https://doi.org/10.1016/B978-0-12-394316-3.00009-0
• Amann, M., & Dempsey, J. A. (2016). Ensemble input of group III/IV muscle afferents to CNS: A limiting factor of central motor drive during endurance exercise from normoxia to moderate hypoxia. Advences in Experimental Medicine and Biology, 903, 325–342. https://doi.org/10.1007/978-1-4899-7678-9_22
• Aspatwar, A., Tolvanen, M. E. E., Schneider, H. P., Becker, H. M., Narkilahti. S., Parkkila. S., & Deitmer. J. W. (2019). Catalytically inactive carbonic anhydrase-related proteins enhance transport of lactate by MCT1. FEBS Open Bio, 9, 1204–11. https://doi.org/10.1002/2211-5463.12647
• Becker, H. M., Hirnet, D., Fecher-Trost, C., Süitemeyer, D., & Deitmer, J. W. (2005). Transport activity of MCT1 expressed in xenopus oocytes is increased by interaction with carbonic anhydrase. Journal of Biological Chemistry, 280, 39882–9. https://doi.org/10.1074/jbc.M503081200
• Benítez‐Muñoz, J. A., Cupeiro, R., Rubio‐Arias, J. Á., Amigo, T., & González‐Lamuño, D. (2024). Exercise influence on monocarboxylate transporter 1 (MCT1) and 4 (MCT4) in the skeletal muscle: A Systematic review. Acta Physiologica, Article e14083. https://doi.org/10.1111/apha.14083
• Billat, V. L., Mouisel, E., Roblot, N., & Melki, J. (2005). Inter and intrastrain variation in mouse critical running speed. Journel of Applied Physiology, 98, 1258–1263. https://doi.org/10.1152/japplphysiol.00991.2004
• Bisbach, C. M., Hass, D. T., Thomas, E. D., Cherry, T. J., & Hurley, J. B. (2022). Monocarboxylate Transporter 1 (MCT1) Mediates Succinate Export in the Retina. Invest Ophthalmol & Visual Science, 63(4), 1-10. https://doi.org/10.1167/iovs.63.4.1
• Bishop, D., Edge, J., Thomas, C., & Mercier. J. (2007). High-intensity exercise acutely decreases the membrane content of MCT1 and MCT4 and buffer capacity in human skeletal muscle. Journal of Applied Physiology, 102(2), 616–21. https://doi.org/10.1152/japplphysiol.00590.2006
• Bishop, D., Edge, J., Mendez-Villanueva, A., Thomas, C., & Schneiker, K. (2009). High-intensity exercise decreases muscle buffer capacity via a decrease in protein buffering in human skeletal muscle. Pflugers Archiv European Journal of Physiology, 458(5), 929–36. https://doi.org/10.1007/s00424-009-0673-z
• Blaszczak, W., Williams, H., & Swietach, P. (2022). Autoregulation of H+/lactate efflux prevents monocarboxylate transport (MCT) inhibitors from reducing glycolytic lactic acid production. British Journal of Cancer, 127(7), 1365-1377. https://doi.org/10.1038/s41416-022-01910-7
• Bonen, A. (2001). The expression of lactate transporters (MCT1 And MCT4) in he- art and muscle. European Journal of Applied Physiology, 86(1), 6–11. https://doi.org/10.1007/s004210100516
• Bonen, A., Heynen, M., & Hatta, H. (2006). Distribution of monocarboxylate transporters MCT1‐MCT8 in rat tissues and human skeletal muscle. Applied Physiology, Nutrition, and Metabolism, 31(1), 31–39. https://doi.org/10.1139/h05-002
• Borthakur, A., Gill, R. K., Hodges, K., Ramaswamy, K., Hecht, G., & Dudeja, P. K. (2006). Enteropathogenic Escherichia coli inhibits butyrate uptake in Caco-2 cells by altering the apical membrane MCT1 level. American Journal of Physiology - Gastrointestinal and Liver Physiology, 290(1), 30–5. https://doi.org/10.1152/ajpgi.00302.2005
• Bosshart, P. D., Kalbermatter, D., Bonetti, S., & Fotiadis, D. (2019). Mechanistic basis of L-lactate transport in the SLC16 solute carrier family. Nature Communications, 10(1), Article 2649. https://doi.org/10.1038/s41467-019-10566-6
• Brown, M. A., & Brooks, G. A. (1994). Trans‐stimulation of lactate transport from rat sarcolemmal membrane vesicles. Archives of Biochemistry and Biophysics, 313(1), 22–28. https://doi.org/10.1006/abbi.1994.1353
• Brooks, G. A. (2018). The science and translation of lactate shuttle theory. Cell Metabolism, 27(4), 757–785. https://doi.org/10.1016/j.cmet.2018.03.008
• Bröer, S., Schneider, H. P., Bröer, A., Rahman, B., Hamprecht, B., & Deitmer, J. W. (1998). Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochemical Journal, 333, 167–74. https://doi.org/10.1042/bj3330167
• Burgomaster, K. A., Cermak, N. M., Phillips, S. M., Benton, C. R.., Bonen, A., & Gibala, M. J. (2007). Divergent response of metabolite transport proteins in human skeletal muscle after sprint interval training and detraining. American Journal of Physiology- Regulatory Integrative and Comparative Physiology, 292(5), 1970–6. https://doi.org/10.1152/ajpregu.00503.2006
• Contreras-Baeza, Y., Sandoval, P.Y., Alarcón, R., Galaz, A., Cortés-Molina, F., Alegría, K., Baeza-Lehnert, F., Arce-Molina, R., Guequén, A., Flores, C. A., San Martín, A., & Barros, L. F. (2019). Monocarboxylate transporter 4 (MCT4) is a high affinity transporter capable of exporting lactate in high-lactate microenvironments. The Journal of Biological Chemistry, 294(52), 20135-20147. https://doi.org/10.1074/jbc.RA119.009093
• Cundy, K. C. (2005). Novel uses of drug transporters for drug delivery: A case study with gabapentin. Drug Transporters in ADME.
• Dimmer, K. S., Friedrich, B., Lang, F., Deitmer, J. W., & Broer, S. (2000). The Low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochemical Journal, 350, 219–27. https://doi.org/10.1042/bj3500219
• Domenech-Estevez, E., Baloui, H., Repond, C., Rosafio, K., Medard, J. J., Tricaud, N., Pellerin, L., & Chrast, R. (2015). Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination. The Journal of Neuroscience, 35(10), 4151–4156. https://doi.org/10.1523/JNEUROSCI.3534-14.2015
• Dubouchaud, H., Butterfield, G. E., Wolfel, E. E., Bergman, B.C., & Brooks, G. A. (2000). Endurance training, expression, and physiology of LDH, MCT1, and MCT4 in human skeletal muscle. American Journal of Physiology - Endocrinology and Metabolism, 278(4), 571–9. https://doi.org/ 10.1152/ajpendo.2000.278.4.E571
• El Hayek, L., Khalifeh, M., Zibara, V., Abi Assaad, R., Emmanuel, N., Karnib N., El-Ghandour, R., Nasrallah, P., Bilen, M., Ibrahim, P., Younes, J., Abou Haidar, E., Barmo, N., Jabre, V., Stephan, J. S., & Süleyman, S. F. (2019). Lactate mediates the effects of exercise on learning and memory through SIRT1-dependent activation of hippocampal brain-derived neurotrophic factor (BDNF). The Journal of Neuroscience, 39(13), 2369–2382. https://doi.org/10.1523/JNEUROSCI.1661-18.2019
• Enoki, T., Yoshida, Y., Lally, J., Hatta, H., & Bonen, A. (2006). Testosterone increases lactate transport, monocarboxylate transporter (MCT) 1 and MCT4 in rat skeletal muscle. The Journal of Physiology, 577(1), 433-443. https://doi.org/10.1113/jphysiol.2006.115436
• Felmlee, M. A., Jones, R. S., Rodriguez-Cruz, V., Follman, K. E., & Morris, M. E. (2020). Monocarboxylate transporters (SLC16): Function, regulation, and role in health and disease. Pharmacological Reviews, 72(2), 466–48. https://doi.org/10.1124/pr.119.018762
• Fisel, P., Schaeffeler, E., & Schwab, M. (2018). Clinical and functional relevance of the monocarboxylate transporter family in disease pathophysiology and drug therapy. Clinical and Translational Science, 11(4), 352-364. https://doi.org/10.1111/cts.12551
• Filiz, K. (1999). Güreşçilerin müsabaka öncesi laktik asit seviyeleri. Beden Eğitimi ve Spor Bilimleri Dergisi, 1, 11-16.
• Freitas, D. A., Rocha-Vieira, E., Soares, B. A., Nonato, L. F., Fonseca, S. R., Martins, J. B., Mendonça, V. A., Lacerda, A.C., Massensini A. R., Poortamns, J. R., Meeusen, R., & Leite, H. R. (2018). High intensity interval training modulates hippocampal oxidative stress, BDNF and inflammatory mediators in rats. Physiol & Behavior, 184, 6-11. https://doi.org/10.1016/j.physbeh.2017.10.027
• Friesema, E. C. H., Ganguly, S., Abdalla, A., Manning Fox, J. E., Halestrap, A. P., & Visser, T. J. (2003). Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. Journal of Biological Chemistry, 278(41), 40128–35. https://doi.org/10.1074/jbc.M300909200
• Forte, L. D. M., de Almeida Rodrigues, N., Cordeiro, A. V., de Fante, T., de Paula Simino, L. A., de Souza Torsoni, A., Torsoni, M.A., Gobatto, C.A., & Barros Manchado-Gobatto, F. (2022). Effect of acute swimming exercise at different intensities but equal total load over metabolic and molecular responses in swimming rats. Journal of Muscle Research and Cell Motility, 43(1), 35-44. https://doi.org/10.1007/s10974-022-09614-4
• Gallagher, S. M., Castorino, J. J., Wang, D., & Philp, N. J. (2007). Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231. Cancer Research, 67(9), 4182–9. https://doi.org/10.1158/0008-5472.CAN-06-3184
• Gao, C., Yang, B., Li, Y., & Pei, W. (2023). A monocarboxylate transporter-dependent mechanism confers resistance to exercise-induced fatigue in a high-altitude hypoxic environment. Scientific Reports, 13(1), 2949. https://doi.org/10.1038/s41598-023-30093-1
• Garcia, C. K., Goldstein, J. L., Pathak, R. K., Anderson, R. G. W., & Brown, M. S. (1994). Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell, 76(5), 865–873. https://doi.org/10.1016/0092-8674(94)90361-1
• Geers, C., & Gros, G. (2000). Carbon dioxide transport and carbonic anhydrase in blood and muscle. Physiological Reviews, 80(2), 681–715. https://doi.org/10.1152/physrev.2000.80.2.681
• Geistlinger, K., Schmidt, J. D., Beitz, E. (2023). Human monocarboxylate transporters accept and relay protons via the bound substrate for selectivity and activity at physiological pH. PNAS Nexus, 2(2), Article pgad007. https://doi.org/10.1093/pnasnexus/pgad007
• Girard, O., & Millet, G. P. (2008). Neuromuscular fatigue in racquet sports. Neurologich Clinics, 26(1), 181–194. https://doi.org/10.1016/j.ncl.2007.11.011
• Goodwin, M. L., Harris, J. E., Hernandez, A., & Gladden, L. B. (2007). Blood lactate measurements and analysis during exercise: A Guide for clinicians. Journal of Diabetes Science and Technology, 1(4), 558–569. https://doi.org/10.1177/193229680700100414
• Halestrap, A. P., & Meredith, D. (2004). The SLC16 gene family - From monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Archiv European Journal of Physiology. 447(5), 619–28. https://doi.org/10.1007/s00424-003-1067-2
• Halestrap, A. P. (2012). The monocarboxylate transporter family–structure and functional characterization. IUBMB Life, 64(1), 1–9. https://doi.org/10.1002/iub.573
• Halestrap, A. P., & Wilson, M. C. (2012). The Monocarboxylate Transporter Family-Role and Regulation. IUBMB Life, 64(2), 109–11. https://doi.org/10.1002/iub.572
• Hargreaves, M., & Spriet, L. L. (2020). Skeletal muscle energy metabolism during exercise. Nature Metabolism, 2(9), 817–828. https://doi.org/10.1038/s42255-020-0251-4
• Hashimoto, T., Masuda, S., Taguchi, S., & Brooks, G. A. (2005). Immunohistochemical analysis of MCT1, MCT2 and MCT4 expression in rat plantaris muscle. The Journal of Physiology, 567, 121–129. https://doi.org/10.1113/jphysiol.2005.087411
• Hashimoto, T., Hussien, R., Oommen, S., Gohil, K., & Brooks, G. A. (2007). Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis. The FASEB Journal, 21(10), 2602–12. https://doi.org/10.1096/fj.07-8174com
• Hazır, T., Açıkada, C. (2005). İskelet ve kalp kaslarında lakti̇k asi̇ti̇n taşınımı: Monokarboksi̇l taşıyıcı protei̇nler Bölüm I. Spor Bilimleri Dergisi, 16(2), 123–12.
• Hu, J., Cai, M., Shang, Q., Li, Z., Feng, Y., Liu B., Xue, X., & Lou, S. (2021). Elevated lactate by high-intensity interval training regulates the hippocampal BDNF expression and the mitochondrial quality control system. Frontiers in Physiology, 12, 629914. https://doi.org/10.3389/fphys.2021.629914
• Jha, M. K., Lee, Y., Russell, K. A., Yang, F., Dastgheyb, R. M., Deme, P., Ament, X, H., Chen, W., Liu, Y., Guan, Y., Polydefkis, M. J., Hoke, A., Haughey, N. J., Rothstein, J. D., & Morrison, B. M. (2019). Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging. Glia, 68(1), 161-177. https://doi.org/10.1002/glia.23710
• Juel, G., & Halestrap, A.P. (1999). Lactate transport in skeletal muscle - Role and regulation of the monocarboxylate transporter. Journal of Physiology, 517, 633–42. https://doi.org/10.1111/j.1469-7793.1999.0633s.x
• Juel, C. (1996). Symmetry and pH dependency of the lactate/proton carrier in skeletal muscle studied with rat sarcolemmal giant vesicles. Biochimica et Biophysica Acta, 1283(1), 106–110. https://doi.org/10.1016/0005-2736(96)00084-3
• Kitaoka, Y., Hoshino, D., & Hatta, H. (2012). Monocarboxylate transporter and lactate metabolism. The Journal of Physical and Fitness and Sports Medicine, 1(2), 247-252. https://doi.org/10.7600/jpfsm.1.247
• Kitaoka, Y., Takeda, K., Tamura, Y., & Hatta, H. (2016). Lactate administration increases mRNA expression of PGC-1alpha and UCP3 in mouse skeletal muscle. Applied Physiology, Nutrition and Metabolism, 41(6), 695–698. https://doi.org/10.1139/apnm-2016-0016
• Kitaoka, Y., Takahashi, K., & Hatta, H. (2022). Inhibition of monocarboxylate transporters (MCT) 1 and 4 reduces exercise capacity in mice. Physiological Reports, 10(17), Article e15457. https://doi.org/10.14814/phy2.15457
• Kobayashi, R., Maruoka, J., Norimoto, H., Ikegaya, Y., Kume, K., & Ohsawa, M. (2019). Involvement of l-lactate in hippocampal dysfunction of type I diabetes. Journal of Pharmacological Science, 141(1), 79–82. https://doi.org/10.1016/j.jphs.2019.09.004
• Lee, Y., Morrison, B. M., Li, Y., Lengacher, S., Farah, M. H., Hoffman, P. N., Liu, Tsingalia, A., Jin, L., Zhang, P. W., Pellerin, L., Magistretti, P. J., & Rothstein, J. D. (2012). Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature, 487(7408), 443‐448. https://doi.org/10.1038/nature11314
• Lev-Vachnish, Y., Cadury, S., Rotter-Maskowitz, A., Feldman, N., Roichman, A., Illouz, T., Varyak, A., Nicola, R., Madar, R., & Okun, E. (2019). L-lactate promotes adult hippocampal neurogenesis. Frontiers in Neuroscience, 13, 403. https://doi.org/10.3389/fnins.2019.00403
• Lin, R. Y., Vera, J. C., Chaganti, R. S. K., & Golde, D. W. (1998). Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter. Journal of Biological Chemistry, 273(44), 28959–65. https://doi.org/10.1074/jbc.273.44.28959
• Marcinek, D. J., Kushmerick, M. J., & Conley, K. E. (2010). Lactic acidosis in vivo: Testing the link between lactate generation and H+ accumulation in ischemic mouse muscle. Journal of Applied Physiology, 108(6), 1479–86. https://doi.org/10.1152/japplphysiol.01189.2009
• Martinez, B. A. (2012). Lactate‐starved neurons in ALS. Disease Models & Mechanismis, 5(6), 711‐712. https://doi.org/10.1242/dmm.010892
• Messonnier, L., Kristensen, M., Juel, C., & Denis, C. (2007). Importance of pH regulation and lactate/H+ transport capacity for work production during supramaximal exercise in humans. Journal of Applied Physiology, 102(5), 1936–44. https://doi.org/10.1152/japplphysiol.00691.2006
• Miller, B. F., Fattor, J. A., Jacobs, K. A., Horning, M. A., Navazio, F., Lindinger, M. I., & Brooks, G. A. (2002). Lactate and glucose interactions during rest and exercise in men: Effect of exogenous lactate infusion. Journal of Physiology, 544(3), 963–75. https://doi.org/10.1113/jphysiol.2002.027128
• Morris, M. E., & Felmlee, M. A. (2008). Overview of the proton-coupled MCT (SLC16A) family of transporters: Characterization, function and role in the transport of the drug of abuse γ-Hydroxybutyric acid. The AAPS Journal, 10(2), 311–32. https://doi.org/10.1208/s12248-008-9035-6
• Morrison, B. M., Lee, Y., & Rothstein, J. D. (2013). Oligodendroglia: Metabolic supporters of axons. Trends in Cell Biology, 23(12), 644‐651. https://doi.org/10.1016/j.tcb.2013.07.007
• Morrison, B. M., Tsingalia, A., Vidensky, S., Lee, Y., Jin, L., Farah, M. H., & Rothstein, J. D. (2015). Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush. Experimental Neurology, 263, 325–338. https://doi.org/10.1016/j.expneurol.2014.10.018
• Moxnes, J. F., & Sandbakk, Ø. (2012). The kinetics of lactate production and removal during whole-body exercise. Theoretical Biology and Medical Modelling, 9, 7. https://doi.org/10.1186/1742-4682-9-7
• Murakami, Y., Kohyama, N., Kobayashi, Y., Ohbayashi, M., Ohtani, H., Sawada, Y., & Yamamoto, T. (2005). Functional characterization of human monocarboxylate transporter 6 (SLC16A5). Drug Metabolism and Disposition, 33(12), 1845–51. https://doi.org/10.1124/dmd.105.005264
• Okamoto, M., Mizuuchi, D., Omura, K., Lee, M., Oharazawa, A., Yook, J. S., Inoue, K., & Soya, H. (2021). High-intensity intermittent training enhances spatial memory and hippocampal neurogenesis associated with BDNF signaling in rats. Cerebral Cortex, 31(9), 4386–4397. https://doi.org/10.1093/cercor/bhab093
• Park. J., Kim, J., & Mikami, T. (2021). Exercise-induced lactate release mediates mitochondrial biogenesis in the hippocampus of mice via monocarboxylate transporters. Frontiers in Physiology, 16(12), 736905. https://doi.org/10.3389/fphys.2021.736905
• Philips, S. (2015). Fatigue in sport and exercise. Routledge.
• Philips, T., & Rothstein, J. D. (2014). Glial cells in amyotrophic lateral sclerosis. Experimental Neurology, 262, 111‐120. https://doi.org/10.1016/j.expneurol.2014.05.015
• Poole, R. C., & Halestrap, A. P. (1994). N-terminal protein sequence analysis of the rabbit erythrocyte lactate transporter suggests identity with the cloned monocarboxylate transport protein MCT1. The Biochemical Journel, 303(3), 755–759. https://doi.org/10.1042/bj3030755
• Prag, H. A., Gruszczyk, A. V., Huang, M. M., Beach, T. E., Young, T., Tronci, L., Nikitopoulou, E., Mulvey, J. F., Ascione, R., Hadjihambi, A., Shattock, M. J., Pellerin, L., Saeb-Parsy, K., Frezza, C., James, A. M., Krieg, T., Murphy, M. P., & Aksentijević, D. (2020). Mechanism of succinate efflux upon reperfusion of the ischemic heart. Cardiovascular Research, 117(4), 1188–1201. https://doi.org/10.1093/cvr/cvaa148
• Reddy, A., Bozi, L. H. M., Yaghi, O. K., Mills, E. L., Xiao, H., Nicholson, H. E., Paschini, M., Paulo, J. A., Garrity, R., Laznik-Bogoslavski, D., Ferreira, J. C.B., Carl, C. S., Sjøberg, K. A., Wojtaszewski, J. F.P., Jeppesen, J. F., Kiens, B., Gygi, S. P., Richter, E. A., Mathis, D., & Chouchani, E. T. (2020). pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise. Cell, 183(1), 62-75. https://doi.org/10.1016/j.cell.2020.08.039
• Rinholm, J. E., Hamilton, N. B., Kessaris, N., Richardson, W.D., Bergersen, L. H., & Attwell, D. (2011). Regulation of oligodendrocyte development and myelination by glucose and lactate. The Journal of Neuroscience, 31(2), 538‐548. https://doi.org/10.1523/JNEUROSCI.3516-10.2011
• Riske L., Thomas R. K., Baker G. B., & Dursun S. M. (2017). Lactate in the brain: an update on its relevance to brain energy, neurons, glia and panic disorder. Therapeutic Advances in Psychopharmacology, 7(2), 85–89. https://doi.org/10.1177/2045125316675579
• Robergs, R. A., Ghiasvand, F., & Parker, D. (2004). Biochemistry of exercise-induced metabolic acidosis. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 287(3), 502–16. https://doi.org/10.1152/ajpregu.00114.2004
• Rowe, G. C., Patten, I. S., Zsengeller, Z. K., El-Khoury, R., Okutsu, M., Bampoh S., Koulisis, N., Farrell, C., Hirshman, M. F., Yan, Z., Goodyear, L. J., Rustin, P., & Arany Z. (2013). Disconnecting mitochondrial content from respiratory chain capacity in PGC-1-deficient skeletal muscle. Cell Reports, 3(5), 1449–1456. https://doi.org/10.1016/j.celrep.2013.04.023
• Jones, R.S., & Morris, M. E. (2016). Monocarboxylate Transporters: Therapeutic Targets and Prognostic Factors in Disease. Clinical Pharmacology and Therapeutics, 100(5), 454–463. https://doi.org/10.1002/cpt.418
• Rusu, V., Hoch, E., Mercader, J. M., Tenen, D. E., Hartigan, C. R., Deran, M., von Grotthuss, M., Fontanillas, P., Spooner, A., Guzman, G., Deik, A. A., Pierce, K. A., Dennis, C., Clish, C. B., Carr, S. A., Wagner, B. K., Schenone, M., Ng MCY, Chen, B. H., Centeno-Cruz, F., Zerrweck, C., Orozco, L., Altshuler, D. M., Schreiber, S. L., Florez, J. C., Jacobs, S. B. R., & Lander, E. S. (2018). Type 2 diabetes variants disrupt function of SLC16A11 through two distinct mechanisms. Cell, 170(1), 199–212. https://doi.org/10.1016/j.cell.2017.06.011
• Sarı, R., Demirkan, E., & Kaya, M. (2016). Farklı toparlanma uygulamalarının yüzücülerde laktik asit düzeyine etkisinin incelenmesi. Journal of Contemporary Medicine, 6(4), 327–33. https://doi.org/10.16899/ctd.59324
• Seyedi, R., Tayebi, S. M., Zhang, D., & Yiming, Q. (2023). The Role of monocarboxylate transporter-1 and -4 in exercise and training: A Mini-review article. Science & Sports, 39(2), 144-152. https://doi.org/10.1016/j.scispo.2022.11.009
• K. Powers, S., & T. Howley, E. (2017). Exercise Physiology: Theory and Application to Fitness and Performance. McGraw-Hill Education.
• Secher, N. H., Quistorff, B., & Dalsgaard, M. K. (2006). The Muscles work, but the brain gets tired. Ugeskrift for Laeger. 168(51), 4503–4506.
• Shima, T., Kawabata-Iwakawa, R., Onishi, H., Jesmin, S., & Yoshikawa, T. (2023). Light-intensity exercise improves memory dysfunction with the restoration of hippocampal MCT2 and miRNAs in type 2 diabetic mice. Metabolic Brain Disease, 38(1), 245-254. https://doi.org/10.1007/s11011-022-01117-y
• Stanescu, S., Bravo-Alonso, I., Belanger-Quintana, A., Pérez, B., Medina-Diaz, M., Ruiz-Sala, P., Flores, N. P., Buenache, R., Arrieta, F., & Rodríguez-Pombo, P. (2022). Mitochondrial bioenergetic is impaired in Monocarboxylate transporter 1 deficiency: a new clinical case and review of the literature. Orphanet Journal of Rare Diseases, 17(1), 1-11. https://doi.org/10.1186/s13023-022-02389-4
• Takahashi, K., Kitaoka, Y., Yamamoto, K., Matsunaga, Y., & Hatta, H. (2019). Effects of lactate administration on mitochondrial enzyme activity and monocarboxylate transporters in mouse skeletal muscle. Physiological Reports, 7(17), Article e14224. https://doi.org/10.14814/phy2.14224
• Takahashi, K., Kitaoka, Y., Yamamoto, K., Matsunaga, Y., & Hatta, H. (2020). Oral lactate administration additively enhances endurance training-induced increase in cytochrome C oxidase activity in mouse soleus muscle. Nutrients, 12(3), 770. https://doi.org/10.3390/nu12030770
• Takebe, K., Nio-Kobayashi, J., Takahashi-Iwanaga, H., & Iwanaga, T. (2008). Histochemical demonstration of a monocarboxylate transporter in the mouse perineurium with special reference to GLUT1. Biomedical Research, 29(6), 297–306. https://doi.org/10.2220/biomedres.29.297
• Thomas, C., Perrey, S., Lambert, K., Hugon, G., Mornet, D., & Mercier, J. (2005). Monocarboxylate transporters, blood lactate removal after supramaximal exercise, and fatigue indexes in humans. Journal of Applied Physiology, 98(3), 804–9. https://doi.org/10.1152/japplphysiol.01057.2004
• Thomas, C., Bishop, D. J., Lambert, K., Mercier, J., & Brooks, G. A. (2012). Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: Current status. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 302(1), 14. https://doi.org/10.1152/ajpregu.00250.2011
• Thomas, C., Delfour‐Peyrethon, R., Lambert, K., Granata, C., Hobbs, T., Hanon, C., & Bishop, D. J. (2023). The effect of pre-exercise alkalosis on lactate/pH regulation and mitochondrial respiration following sprint-interval exercise in humans. Frontiers in Physiology, 14, 71. https://doi.org/10.3389/fphys.2023.1073407
• Tsiani, E., Lekas, P., George Fantus, I., Dlugosz, J., & Whiteside, C. (2002). Increases in muscle MCT are associated with reductions in muscle lactate after a single exercise session in humans. American Journal of Physiology - Endocrinology and Metabolism, 282(1), 154–60. https://doi.org/10.1152/ajpendo.2002.282.1.E154
• Vancamp, P., Demeneix, B. A., & Remaud, S. (2020). Monocarboxylate transporter 8 deficiency: Delayed or permanent hypomyelination?. Frontiers Endocrinology (Lausanne), 13(11), 283. https://doi.org/10.3389/fendo.2020.00283
• Van Hall, G. (2010). Lactate kinetics in human tissues at rest and during exercise. Acta Physiologica (Oxford, England), 199(4), 499–508. https://doi.org/10.1111/j.1748-1716.2010.02122.x
• Visser, W. E., Friesema, E. J., Jansen, J., & Visser, T. J. (2007). Thyroid hormone transport by monocarboxylate transporters. Best practice & research. Clinical Endocrinology & Metabolism, 21(2), 223–236. https://doi.org/10.1016/j.beem.2007.03.008
• Wilson, M. C., Meredith, D., & Halestrap, A. P. (2002). Fluorescence resonance energy transfer studies on the interaction between the lactate transporter MCT1 and CD147 provide information on the topology and stoichiometry of the complex in Situ. Journal of Biological Chemistry, 277(5), 3666–72. https://doi.org/10.1074/jbc.M109658200
• Zhang, B., Jin, Q., Xu, L., Li, N., Meng, Y., Chang, S., Zheng, X., Wang, J., Chen, Y., Neculai, D., Gao, N., Zhang, X., Yang, F., Guo, J., & Ye, S. (2020). Cooperative transport mechanism of human monocarboxylate transporter 2. Nature Communications, 11(1), 2429. https://doi.org/10.1038/s41467-020-16334-1
• Zhou, P., Guan, T., Jiang, Z., Namaka, M., Huang, Q. J., & Kong, J. M. (2017). Monocarboxylate transporter 1 and the vulnerability of oligodendrocyte lineage cells to metabolic stresses. CNS Neuroscience & Therapeutics, 24(2), 1–9. https://doi.org/10.1111/cns.12782
• Zhu, S., Goldschmidt-Clermont, P. J., & Dong, C. (2005). Inactivation of monocarboxylate transporter MCT3 by DNA methylation in atherosclerosis. Circulation, 112, 1353–61. https://doi.org/10.1161/CIRCULATIONAHA.104.519025