title: Identification of glucose-6-phosphate transporter as a key regulator functioning at the autophagy initiation step.
abstract: 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.
authors.affiliation: Global Research Laboratory, School of Biological Science, Seoul National University, Gwanak-gu, Seoul, Republic of Korea; Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Gwanak-gu, Seoul, Republic of Korea.
authors.forename: Hye-Hyun
authors.initials: HH
authors.lastname: Ahn
authors.affiliation: Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Global Research Laboratory, School of Biological Science, Seoul National University, Gwanak-gu, Seoul, Republic of Korea.
authors.forename: Huikyong
authors.initials: H
authors.lastname: Lee
authors.affiliation: Global Research Laboratory, School of Biological Science, Seoul National University, Gwanak-gu, Seoul, Republic of Korea.
authors.forename: WonJae
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jae-Woong
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Global Research Laboratory, School of Biological Science, Seoul National University, Gwanak-gu, Seoul, Republic of Korea.
authors.forename: Ha-Kyung
authors.initials: HK
authors.lastname: Pyo
authors.affiliation: Global Research Laboratory, School of Biological Science, Seoul National University, Gwanak-gu, Seoul, Republic of Korea; Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Gwanak-gu, Seoul, Republic of Korea.
authors.forename: Do hyung
authors.initials: do H
authors.lastname: Nah
authors.affiliation: Global Research Laboratory, School of Biological Science, Seoul National University, Gwanak-gu, Seoul, Republic of Korea; Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Gwanak-gu, Seoul, Republic of Korea. Electronic address: ykjung@snu.ac.kr.
authors.forename: Yong-Keun
authors.initials: YK
authors.lastname: Jung
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D000071183:Autophagy-Related Proteins; D002460:Cell Line; D003412:Cricetulus; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D000071058:Huntingtin Protein; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000201:enzymology / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015854:Up-Regulation; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D017920:Antiporters; C574794:ATG9A protein, human; D000071183:Autophagy-Related Proteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D046912:Multiprotein Complexes; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C503531:SLC37A4 protein, human; D033921:Vesicular Transport Proteins; D000071189:Autophagy-Related Protein-1 Homolog; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; C484754:ULK1 protein, human
keywords: ATG9; Autophagy modulator; G6PT; Screening; ULK1