7y1q

Structural highlights

Function

MOT1_MOUSE Bidirectional proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH (By similarity). The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter (By similarity). Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis (PubMed:22522610, PubMed:24367518). Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart. Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 302-Asp is essential for the conformational transition (PubMed:32946811).[UniProtKB:P53985][UniProtKB:P53987]^{[1] [2] [3]}

References

1. ↑ Pullen TJ, Sylow L, Sun G, Halestrap AP, Richter EA, Rutter GA. Overexpression of monocarboxylate transporter-1 (SLC16A1) in mouse pancreatic β-cells leads to relative hyperinsulinism during exercise. Diabetes. 2012 Jul;61(7):1719-25. PMID:22522610 doi:10.2337/db11-1531
2. ↑ 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 Dec 18;8(12):e82505. PMID:24367518 doi:10.1371/journal.pone.0082505
3. ↑ Reddy A, Bozi LHM, Yaghi OK, Mills EL, Xiao H, Nicholson HE, Paschini M, Paulo JA, Garrity R, Laznik-Bogoslavski D, Ferreira JCB, Carl CS, Sjøberg KA, Wojtaszewski JFP, Jeppesen JF, Kiens B, Gygi SP, Richter EA, Mathis D, Chouchani ET. pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise. Cell. 2020 Oct 1;183(1):62-75.e17. PMID:32946811 doi:10.1016/j.cell.2020.08.039