GLUT6 is a lysosomal transporter that is regulated by inflammatory stimuli and modulates glycolysis in macrophages

Shotaro Maedera, Tadahaya Mizuno, Hiromu Ishiguro, Takuya Ito, Tomoyoshi Soga, Hiroyuki Kusuhara

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The solute carrier family is an important protein class governing compound transport across membranes. However, some of its members remain functionally unidentified. We analyzed ChIP-seq data for the NF-κB family transcription factor RelA and identified GLUT6 as a functionally uncharacterized transporter that putatively works in inflammatory responses. Inflammatory stimuli increase GLUT6 expression level, although GLUT6-knockout mice exhibit a subtle phenotype to lipopolysaccharide administration. Metabolomics and in vitro analyses show that GLUT6 functions as a glycolysis modulator in inflammatory macrophages. GLUT6 does not mediate glucose uptake and is localized on lysosomal membranes. We conclude that GLUT6 is a lysosomal transporter that is regulated by inflammatory stimuli and modulates inflammatory responses by affecting the metabolic shift in macrophages.

Original languageEnglish
Pages (from-to)195-208
Number of pages14
JournalFEBS Letters
Volume593
Issue number2
DOIs
Publication statusPublished - 2019 Jan 1

Keywords

  • GLUT6
  • inflammation
  • macrophages

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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