Identification of glucose-6-phosphate transporter as a key regulator functioning at the autophagy initiation step

Hye Hyun Ahn; Yumin Oh; Huikyong Lee; Wonjae Lee; Jae Woong Chang; Ha Kyung Pyo; Do Hyung Nah; Yong Keun Jung

doi:10.1016/j.febslet.2015.05.018

Identification of glucose-6-phosphate transporter as a key regulator functioning at the autophagy initiation step

Hye Hyun Ahn, Yumin Oh, Huikyong Lee, Wonjae Lee, Jae Woong Chang, Ha Kyung Pyo, Do Hyung Nah, Yong Keun Jung

Metabolic and Systems Biology (BMBB)

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2100-2109
Number of pages	10
Journal	FEBS Letters
Volume	589
Issue number	16
DOIs	https://doi.org/10.1016/j.febslet.2015.05.018
State	Published - Jul 20 2015

Bibliographical note

Funding Information:
We thank Dr. M. Noboru (University of Tokyo) for providing m5-7 cell line. This work was supported by the Grants from the Global Research Laboratory Program (GRL, NRF-2010-00341 ) and a CRI Grant ( NRF-2013R1A2A1A01016896 ) funded by the Ministry of Education, Science and Technology (MEST) in Korea.

Publisher Copyright:
© 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Keywords

ATG9
Autophagy modulator
G6PT
Screening
ULK1

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10.1016/j.febslet.2015.05.018

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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.",

keywords = "ATG9, Autophagy modulator, G6PT, Screening, ULK1",

author = "Ahn, {Hye Hyun} and Yumin Oh and Huikyong Lee and Wonjae Lee and Chang, {Jae Woong} and Pyo, {Ha Kyung} and Nah, {Do Hyung} and Jung, {Yong Keun}",

note = "Funding Information: We thank Dr. M. Noboru (University of Tokyo) for providing m5-7 cell line. This work was supported by the Grants from the Global Research Laboratory Program (GRL, NRF-2010-00341 ) and a CRI Grant ( NRF-2013R1A2A1A01016896 ) funded by the Ministry of Education, Science and Technology (MEST) in Korea. Publisher Copyright: {\textcopyright} 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.",

year = "2015",

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doi = "10.1016/j.febslet.2015.05.018",

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AU - Ahn, Hye Hyun

AU - Oh, Yumin

AU - Lee, Huikyong

AU - Lee, Wonjae

AU - Chang, Jae Woong

AU - Pyo, Ha Kyung

AU - Nah, Do Hyung

AU - Jung, Yong Keun

N1 - Funding Information: We thank Dr. M. Noboru (University of Tokyo) for providing m5-7 cell line. This work was supported by the Grants from the Global Research Laboratory Program (GRL, NRF-2010-00341 ) and a CRI Grant ( NRF-2013R1A2A1A01016896 ) funded by the Ministry of Education, Science and Technology (MEST) in Korea. Publisher Copyright: © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

PY - 2015/7/20

Y1 - 2015/7/20

N2 - 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.

AB - 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.

KW - ATG9

KW - Autophagy modulator

KW - G6PT

KW - Screening

KW - ULK1

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Identification of glucose-6-phosphate transporter as a key regulator functioning at the autophagy initiation step

Abstract

Bibliographical note

Keywords

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