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 journalArticle

11 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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