ArticleNature communications2020
Cooperative transport mechanism of human monocarboxylate transporter 2.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 54 citations in OpenAlex.
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Monocarboxylate Transporter 2 (MCT2) Reduction Is Associated with Increased Lung Tumor Growth and Alterations in the Immune Microenvironment in a Subcutaneous Tumor Model.International journal of molecular sciences · 2026Article
- The evolving landscape of the Warburg effect in gastric cancer: From molecular mechanisms to targeted therapy.Clinical and translational medicine · 2026Review
- Lactate dynamics in Parkinson's disease: striatal circuit vulnerability, biomarker potential, and therapeutic windows.Molecular medicine (Cambridge, Mass.) · 2026Review
- Phenylalanine Versus Tyrosine (Pos. 367/332 in MCT1/MCT4) in the Substrate Binding Site Defines Affinity and Preferred Directionality of Human Monocarboxylate Transporters 1-4.Acta physiologica (Oxford, England) · 2026Article
- Higher-order structural organization of mitochondrial metabolism.The Journal of biological chemistry · 2026Review
- Structures of the human glucose-6-phosphate transporter provide insights into its transport cycle and substrate recognition.PLoS biology · 2026Article
- Beyond a metabolite: lactate and lactylation in lung diseases.Respiratory research · 2026Review
- Article
- In silico modeling of anterior foregut endoderm differentiation towards lung epithelial progenitors.NPJ systems biology and applications · 2026Article
- Intrinsic Asymmetry in Weak Acid Transmembrane Transporters.Biomolecules · 2026Review
- Article
- Transport mechanism and drug discovery of human monocarboxylate transporter 1.Acta pharmacologica Sinica · 2025Article
- RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural insights into thyroid hormone transporter MCT8.Nature communications · 2025Article
- Unlocking the secrets of glucose metabolism reprogramming: the role in pulmonary diseases.Frontiers in pharmacology · 2025Review
- Identification of Key Glycolysis-Related Genes in Osteoarthritis and Their Correlation with Immune Infiltration Using Bioinformatics Analysis and Machine Learning.Open access rheumatology : research and reviews · 2025Article
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The utilization of N-acetylgalactosamine and its effect on the metabolism of amino acids in Erysipelotrichaceae strain.BMC microbiology · 2024Article
- Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proton-linked monocarboxylate transporters (MCTs) must transport monocarboxylate efficiently to facilitate monocarboxylate efflux in glycolytically active cells, and transport monocarboxylate slowly or even shut down to maintain a physiological monocarboxylate concentration in glycolytically inactive cells. To discover how MCTs solve this fundamental aspect of intracellular monocarboxylate homeostasis in the context of multicellular organisms, we analyzed pyruvate transport activity of human monocarboxylate transporter 2 (MCT2). Here we show that MCT2 transport activity exhibits steep dependence on substrate concentration. This property allows MCTs to turn on almost like a switch, which is physiologically crucial to the operation of MCTs in the cellular context. We further determined the cryo-electron microscopy structure of the human MCT2, demonstrating that the concentration sensitivity of MCT2 arises from the strong inter-subunit cooperativity of the MCT2 dimer during transport. These data establish definitively a clear example of evolutionary optimization of protein function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.