The Plasma Membrane Lactate Transporter MCT4, but Not MCT1, Is Up-regulated by Hypoxia through a HIF-1α-dependent Mechanism

The monocarboxylate transporter MCT4 mediates lactic acid efflux from most tissues that are dependent on glycolysis for their ATP production. Here we demonstrate that expression of MCT4 mRNA and protein was increased >3-fold by a 48-h exposure to 1% O2, whereas MCT1 expression was not increased. The effect was mimicked by CoCl2 (50 μm), suggesting transcriptional regulation by hypoxia-inducible factor 1α (HIF-1α). The predicted promoters for human MCT1, MCT2, and MCT4 were cloned into the pGL3 vector and shown to be active (luciferase luminescence) under basal conditions. Only the MCT4 promoter was activated (>2-fold) by hypoxia. No response was found in cells lacking HIF-1α. Four potential hypoxia-response…

• A
  AstraZeneca
• BH
  British Heart Foundation
• UO
  University of Oxford