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GLUT6 is a lysosomal transporter that is regulated by inflammatory stimuli and modulates glycolysis in macrophages
Author(s) -
Maedera Shotaro,
Mizuno Tadahaya,
Ishiguro Hiromu,
Ito Takuya,
Soga Tomoyoshi,
Kusuhara Hiroyuki
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13298
Subject(s) - transporter , lipopolysaccharide , microbiology and biotechnology , glycolysis , inflammation , phenotype , transcription factor , solute carrier family , knockout mouse , chemotaxis , biology , chemistry , in vitro , glucose transporter , biochemistry , gene , immunology , metabolism , endocrinology , receptor , insulin
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.