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Identification of glucose‐6‐phosphate transporter as a key regulator functioning at the autophagy initiation step
Author(s) -
Ahn Hye-Hyun,
Oh Yumin,
Lee Huikyong,
Lee WonJae,
Chang Jae-Woong,
Pyo Ha-Kyung,
Nah Do hyung,
Jung Yong-Keun
Publication year - 2015
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 - 10.1016/j.febslet.2015.05.018
Subject(s) - regulator , autophagy , transporter , phosphate , key (lock) , chemistry , identification (biology) , biochemistry , glucose transporter , microbiology and biotechnology , biology , endocrinology , gene , insulin , apoptosis , ecology , botany
Autophagy is a catabolic process involving autophagosome formation via lysosome. However, the initiation step of autophagy is largely unknown. We found an interaction between ULK1 and ATG9 in mammalian cells and utilized the interaction to identify novel regulators of autophagy upstream of ULK1. We established a cell‐based screening assay employing bimolecular fluorescence complementation. By performing gain‐of‐function screening, we identified G6PT as an autophagy activator. G6PT enhanced the interaction between N‐terminal Venus‐tagged ULK1 and C‐terminal Venus‐tagged ATG9, and increased autophagic flux independent of its transport activity. G6PT negatively regulated mTORC1 activity, demonstrating that G6PT functions upstream of mTORC1 in stimulating autophagy.